Arboviruses are infections caused by arboviruses that may be either symptomatic or asymptomatic, according to individuals' resistance and immune response, which dietary patterns can influence. Thus, this study aimed to investigate the possible association between the occurrence of clinical manifestations of arboviruses and the dietary pattern of the population studied. The study was conducted in a rural population in the metropolitan area of Belém, Pará State, Brazil. The sampling consisted of 95 individuals during a febrile outbreak. Two investigations were conducted: clinical-epidemiological-dietary and laboratory investigation based on blood samples taken for arbovirus analysis. Out of the 95 individuals studied, more than half (57.89%) showed clinical manifestations. Following the laboratory serology (HI and IgM ELISA) analyses, viral isolation in C6/36 cells, and viral genome detection (RT-qPCR), the final diagnosis of the cases was 47.37% Oropouche Fever, 2.11% Oropouche Fever and Chikungunya Fever, and 1.05% Mayaro Fever. Regarding dietary pattern, as for the comparison analyses, statistical significance was observed between dietary pattern and classification regarding the presence of symptoms (p<0.05); after the correspondence analysis, symptomatic cases were more associated with a bad dietary pattern, while asymptomatic cases were more associated with a good dietary pattern.

Crimean-Congo hemorrhagic fever virus (CCHFV), a member of the Nairoviridae family and Bunyavirales order, is transmitted to humans via tick bites or contact with the blood of infected animals. It can cause severe symptoms, including hemorrhagic fever, with a mortality rate between 5 to 30%. CCHFV is classified as a high-priority pathogen by the World Health Organization (WHO) due to its high fatality rate and the absence of effective medical countermeasures. CCHFV is endemic in several regions across the world, including Africa, Europe, the Middle East, and Asia, and has the potential for global spread. The emergence of the disease in new areas, as well as the presence of the tick vector in countries without reported cases, emphasizes the need for preventive measures should be taken. In the past, the lack of a suitable animal model susceptible to CCHFV infection has been a major obstacle in the development of vaccines and treatments. However, recent advances in biotechnology and the availability of suitable animal models have significantly expedited the development of vaccines against CCHF. These advancements have not only contributed to an enhanced understanding of the pathogenesis of CCHF but have also facilitated the evaluation of potential vaccine candidates. This review outlines of the immune response to CCHFV and animal models utilized for the study of CCHFV and highlights the progress made in CCHFV vaccine studies. Despite remarkable advancements in vaccine development for CCHFV, it remains crucial to prioritize continued research, collaboration, and investment in this field.

Dengue hemorrhagic fever is an arboviral infectious disease that has occurred frequently as an extraordinary event due to its fast spread and lethal potential in Indonesia. The vector Aedes aegypti is sensitive to climate variability. This study determines the relationship between climate variability and dengue hemorrhagic fever in Surabaya, East Java, Indonesia from 2009 to 2017. This study used the monthly dengue hemorrhagic fever incidence obtained from the Surabaya Health Office and the monthly climate variability parameters (average temperature, rainfall, humidity) obtained from the Indonesian Agency for Meteorology, Climatology and Geophysics and website www.worldweatheronline.com. Data analysis was done using One-Sample Kolmogorov Smirnov Test and Spearman non-parametric correlation test. The results showed a correlation between all three climate variability parameters with dengue hemorrhagic fever incidence (average temperature p<0.05, r=-0.603; rainfall p<0.05, r=0.407; humidity p<0.05, r=0.7). Average temperature is negatively correlated to dengue hemorrhagic fever incidence, while rainfall and humidity are positively correlated to dengue hemorrhagic fever incidence. This study shows preliminary evidence on the correlation of climate variability and dengue hemorrhagic fever in Surabaya, East Java, Indonesia.

Dengue hemorrhagic fever is an arboviral infectious disease that has occurred frequently as an extraordinary event due to its fast spread and lethal potential in Indonesia. The vector Aedes aegypti is sensitive to climate variability. This study determines the relationship between climate variability and dengue hemorrhagic fever in Surabaya, East Java, Indonesia from 2009 to 2017. This study used the monthly dengue hemorrhagic fever incidence obtained from the Surabaya Health Office and the monthly climate variability parameters (average temperature, rainfall, humidity) obtained from the Indonesian Agency for Meteorology, Climatology and Geophysics and website www.worldweatheronline.com. Data analysis was done using One-Sample Kolmogorov Smirnov Test and Spearman non-parametric correlation test. The results showed a correlation between all three climate variability parameters with dengue hemorrhagic fever incidence (average temperature p<0.05, r=-0.603; rainfall p<0.05, r=0.407; humidity p<0.05, r=0.7). Average temperature is negatively correlated to dengue hemorrhagic fever incidence, while rainfall and humidity are positively correlated to dengue hemorrhagic fever incidence. This study shows preliminary evidence on the correlation of climate variability and dengue hemorrhagic fever in Surabaya, East Java, Indonesia.

Mammarenavirus Wenzhouense (WENV) is broadly distributed in Asia, while the he dynamics process of WENV infection remains unclear. A field derived strain of WENV was used to inoculate Sprague-Dawley (SD) rats by intramuscular injection, the process of virus infection was de-tected by controlling time for 28 days. Viral RNA became detectable in the blood at 3 d pi, and remained detectable for about 12 d. In most organ tissues, viral RNA peaked at 7 d pi, then began to decline by 14 d, however remained detectable in intestine and brain tissues at 21 and 28 d pi. Virus shedding had been detected from fecal samples for 5 days from 6 to 11 d pi using qRT-PCR, and was recovered from feces collected at 8 d pi. Horizontal contact infection occurred among cage-mates at 14 and 21 d pi. Antibodies against the nucleocapsid were detected at 5 dpi, next increased and persisted until the end of experiment. The results enabled to discriminate the kinetic of viremic response, virus shedding in feces and horizontal transmission, as well as the potential sites for WENV replication or maintenance of the virus in nature.

The B169L protein (pB169L) of African swine fever virus (ASFV) is a structural protein with an unidentified function during the virus replication. The sequences of the B169L gene and the downstream B438L gene are separated by short intergenic regions. However, the regulatory mode of the gene transcription remains unknown. Here, we identified two distinct promoter regions and two transcription start sites (TSS) located upstream of the open reading frame (ORF) of B438L. Using the promoter reporter system, we demonstrated that the cis activity of the ORF proximal promoter exhibited significantly higher levels compared with that of the distal promoter located in the B169L gene. Furthermore, transfection with the plasmids with two different promoters for B438L could initiate the transcription and expression of the B438L gene in HEK293T cells, and the cis activity of the ORF proximal promoter also displayed the higher activities compared with the distal promoter. Interestingly, the B438L distal promoter also initiated the transcription of the alternatively spliced B169L mRNA (B169L mRNA2) encoding a truncated pB169L (tpB169L) (amino acids 92–169), and the gene transcription efficiency was increased upon mutation of the initiation codon located upstream of the alternatively spliced B169L gene. Taken together, we demonstrated that the distal promoter of B438L gene initiates the transcription of both the B438L mRNA and B169L mRNA2. Comprehensive analysis of the transcriptional regulatory mode of the B438L gene is beneficial for the understanding of the association of B438L protein and pB169L and the construction of the gene-deleted ASFV.

Omsk hemorrhagic fever virus (OHFV) is a member of the tick-borne encephalitis virus (TBEV) complex of the Flaviviridae family. Currently, there is no data on cross-reactivity of antibodies to the NS1 proteins of OHFV and TBEV. Such data are of major interest for monitoring viral encephalitis of unknown etiology due to the increasing geographical distribution of OHFV. In this study, recombinant OHFV NS1 protein was produced using Escherichia сoli expression system and purified. The recombinant OHFV NS1 protein was recognized by specific mice immune ascetic fluids to the native OHFV NS1 protein. Western blot analysis and ELISA of recombinant NS1 proteins of OHFV and TBEV were used to study the cross-reactivity of antibodies from immune ascites fluid obtained from OHFV-infected mice and mAbs against TBEV NS1. Anti-TBEV NS1 mouse monoclonal antibodies (mAbs) have been shown not to be cross-reactive to OHFV NS1 protein. Sera from patients with confirmed tick-borne encephalitis (TBE) were examined by ELISA using recombinant OHFV NS1 and TBEV NS1 proteins as antigens. It was shown for the first time that cross-reactive antibodies to OHFV NS1 protein were not detected in the sera of TBE patients whereas the sera contained antibodies to TBEV NS1 protein.

Crimean-Congo hemorrhagic fever virus is one the most important and wide spread tick-borne viruses. Very little is known about the transmission from the tick and the early aspects of pathogenesis. Here, we generate human cutaneous antigen presenting cells: dermal dendritic cells and Langerhans cells, from umbilical cord progenitor cells. In order to mimic the environment created during tick feeding, tick salivary gland extract was generated from semi-engorged Hyalomma marginatum ticks. Our findings indicate that human dermal dendritic cells and Langerhans cells are susceptible and permissive to Crimean-Congo hemorrhagic fever virus infection, however, to different degrees. Infection leads to cell activation and cytokine/chemokine secretion, although these responses vary between the different cell types. Hyalomma marginatum salivary gland extract had minimal effect on cell responses, with some synergy with viral infection with respect to cytokine secretion. However, salivary gland extract appeared to inhibit antigen presenting cell (APC) migration. Based on the findings here we hypothesize that human dermal dendritic cells and Langerhans cells serve as early target cells. Rather affecting Crimean-Congo hemorrhagic fever virus replication, tick saliva likely immunomodulates and inhibits migration of these APC from the feeding site.

Orthohantaviruses can cause two types of human infections: hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS). HFRS is a zoonotic disease transmitted by multiple rodent species. Yunnan Province in southwest China is the natural foci of HFRS, and Dali Prefecture in Yunnan Province has the highest incidence of HFRS; however, the precise status of orthohantavirus infection in Dali Prefecture remains unknown. To this end, we obtained clinical data of HFRS patients from the medical records of the People's Hospital of Xiangyun County in Dali Prefecture from July 2019 to August 2021. We collected epidemiological data of HFRS patients through interviews and investigated host animals using the night clip or night cage method. We systematically performed epidemiological analyses of patients and host animals. The differences in the presence of rodent activity at home (2=8.75, P=0.031&lt;0.05), of rodent-proof equipment in the food (2=9.19, P=0.025&lt;0.05), and of rodents or rodent excrement in the workplace (2=10.35, P=0.014&lt;0.05) were statistically different in the four clinical types, including mild, medium, severe, and critical HFRS-associated diseases. Furthermore, we conducted molecular detection of orthohantavirus in host animals. The total orthohantavirus infection rate of rodents was 2.7% (9/331); the specific infection rate of specific animal species was 6.1% (5/82) for the Apodemus chevrieri, 100% (1/1) for the Rattus nitidus, 3.8% (2/53) for the Rattus norvegicus, and 12.5% (1/8) for the Crocidura dracula. In this study, a total of 21 strains of orthohantavirus were detected in patients and rodents. The 12 orthohantavirus strains from patients showed a closer relationship with Seoul orthohantavirus (SEOOV) L0199, DLR2, and GZRn60 strains; the six orthohantavirus strains from Rattus norvegicus and Apodemus chevrieri were closely related to SEOOV GZRn60 strain; One strains (XYRn163) from Rattus norvegicus and one strain (XYR.nitidus97) from Rattus nitidus were closely related to SEOOV DLR2 strain; the orthohantavirus strain from Crocidura dracula was closely related to the Luxi orthohantavirus (LUXV) LX309 strain. In conclusion, patients with HFRS in Xuangyun County of Dali Prefecture are predominantly affected by SEOOV, with multiple genotypes of orthohantavirus in host animals, and most importantly, these orthohantavirus strains constantly demonstrated zoonotic risk in humans.

The detection, characterization, and monitoring of SARS-CoV-2 recombinant variants is a challenge to public health authorities worldwide. Recombinant variants, composed of two or more SARS-CoV-2 lineages, often have unknown impacts on transmission, immune escape, and virulence in the early stages of emergence. We examined 4,213 SARS-CoV-2 recombinant SARS-CoV-2 genomes collected between 2020 and 2022 from California to describe regional and statewide trends in prevalence. Many of these recombinant genomes, such as those belonging to the XZ lineage, or novel recombinant lineages, likely originated within the state of California. We discuss the challenges and limitations surrounding Pango lineage assignments, the use of publicly available sequence data, and adequate sample sizes for epidemiologic analyses. Although these challenges will continue as SARS-CoV-2 sequencing volumes decrease globally, this study enhances our understanding of SARS-CoV-2 recombinant genomes to date while providing a foundation for future insights into emerging recombinant lineages.

In Cameroon, Aedes mosquitoes transmit various arboviruses, posing significant health risks. We aimed to characterize the Aedes virome in southwestern Cameroon and identify potential core viruses which might be associated with vector competence. A total of 398 Aedes mosquitoes were collected from four locations (Bafoussam, Buea, Edea and Yaounde). Aedes albopictus dominated all sites except for Bafoussam where Aedes africanus prevailed. Metagenomic analyses of mosquitoes grouped per species into 54 pools revealed notable differences in eukaryotic viromes between Ae. africanus and Ae. albopictus, with the former exhibiting greater richness and diversity. Thirty-seven eukaryotic virus species from 16 families were identified, including six novel viruses with near complete genome sequences. Seven viruses were further quantified in individual mosquitoes via qRT-PCR. Although none of them could be identified as core viruses, Guangzhou sobemo-like virus and Bafoussam mosquito solemovirus virus were highly prevalent regionally in Ae. albopictus and Ae. africanus, respectively. This study highlights the diverse eukaryotic virome of Aedes species in southwestern Cameroon. Despite their shared Genus, Aedes species exhibit limited viral sharing, with varying viral abundance and prevalence across locations. Ae. africanus, an understudied vector, harbors a rich and diverse virome, suggesting potential implications for arbovirus vector competence.

Crimean-Congo haemorrhagic fever virus (CCHFV) is the most geographically widespread tick-borne virus. However, African strains are poorly represented in sequence databases. In addition, almost all sequence data have been obtained from cases of human disease, while information regarding circulation of the virus in tick and animal reservoirs is severely lacking. Here, we characterise the complete coding region of a novel CCHFV strain, detected in African blue ticks (Rhipicephalus (Boophilus) decoloratus) feeding on cattle in an abattoir in Kampala, Uganda. These cattle originated from a farm in Mbarara, a major cattle-trading hub for much of Uganda. Phylogenetic analysis indicates that the newly sequenced strain belongs to the African genotype II clade, which predominantly contains the sequences of strains isolated from West Africa in the 1950’s and South Africa in the 1980’s. Whilst, the viral S (nucleoprotein) and L (RNA polymerase) genome segments shared >90% nucleotide similarity with previously reported genotype II strains, the glycoprotein-coding M segment shared only 80% nucleotide similarity with the next most closely related strains, which were from India and China. This segment also displayed a large number of non-synonymous mutations previously unreported in genotype II strains. Characterisation of this novel strain adds to our limited understanding of the natural diversity of CCHFV circulating in both ticks and in Africa. Such data can be used to inform the design of vaccines and diagnostics, as well as studies exploring the epidemiology and evolution of the virus for the establishment of future CCHFV control strategies.

Hereditary Hemorrhagic Telangiectasia (HHT), also known as Osler-Weber-Rendu syndrome, is a rare and inherited vascular disorder, characterized by the development of arteriovenous malformations (AVMs) in various organs and telangiectasia (small AVM) in the mucocutaneous. The majority of HHT patients have haploinsufficiency of genes involved in the transforming growth factor-beta (TGFβ) signaling pathway, including endoglin (ENG), activin receptor-like kinase 1 (ALK1, also known as ACVRL1), or SMAD4. Active angiogenesis is also required for telangiectasia and AVM development. Anti-angiogenic strategies have been tested in patients and animal models extensively. However, the exact mechanisms for telangiectasia and AVM development remain unclear. In this review, we discuss recent advances in identifying disease mechanisms, and potential therapeutic targets.

Crimean Congo hemorrhagic fever virus (CCHFV) is the causative agent of a globally-spread tick-borne zoonotic infection with an eminent risk of fatal human disease. Imminent public health threat posed by disseminated virus activity and lack of an approved therapeutic make CCHFV an urgent target for vaccine development. We described the construction of a DNA vector expressing nucleocapsid protein (N) of CCHFV (pV-N13) and investigated its potential to stimulate cytokine and total/specific antibody responses in BALB/c and challenge experiment in IFNAR-/- mice. Due to lack of sufficient antibody stimulation towards N protein, we have selected CD24 protein as a potential adjuvant which has proliferative effect on B and T cells. Overall, our N expressing construct when administered solely or in combination with pCD24 vector elicited significant cellular and humoral responses in BALB/c, despite variations in particular cytokines and total antibodies. However, the stimulated antibodies produced due to expression of N protein have shown no neutralizing ability in VNA. Furthermore, challenge experiments were revealed protection potential of N expressing construct in IFNAR -/- mice model. In conclusion, we have shown that CD24 has prominent effect as a genetic adjuvant when co-delivers with a synergic foreign gene expressing vector. Besides, targeting of S segment of CCHFV can be considered as a practical way in developing vaccine against this virus due to its ability to induce immune response which leads to protection in challenge assays in IFN-gamma defective mice models.

Candidate vaccines against African swine fever virus (ASFV) based on naturally attenuated or genetically modified viruses have the potential to generate protective immune responses, although there is no consensus on what defines a protective immune response against ASFV. Studies, espe-cially in sensible host species, focused on unravelling protective mechanisms will contribute to the development of safer and more effective vaccines. The present study provides a detailed analysis of phenotypic and functional data on cellular responses induced by intradermal immunization and subsequent boosting of domestic pigs with the naturally attenuated field strain Lv17/WB/Rie1, as well as the mechanisms underlying protection against intramuscular challenge with the virulent genotype II Armenia/07 strain. The transient mild to moderate increase of IL-8 and IL-10 in serum observed after immunization might be directly correlated with survival. Protection was also associated with a robust ASFV-specific polyfunctional memory T cell response, where CD4CD8 and CD8 T cells were identified as the main cellular sources of virus-specific IFNγ and TNFα. In parallel to cytokine response, these T-cell subsets also showed specific cytotoxic activity as evidenced by the increased expression of the CD107a degranulation marker. Along with virus-specific multifunctional CD4CD8 and CD8 T responses, the increased levels of antigen experienced cytotoxic CD4 T cells observed after challenge in immunized pigs might also contribute to control virulent infection by killing mechanisms targeting infected antigen-presenting cells. Future studies should elucidate whether the memory T-cell responses evidenced in the present study persist and provide long-term protection against further ASFV infections.

In tropical developing regions, typhoid fever and malaria often co-occur, posing serious health risks. The two illnesses have similar symptoms, which makes diagnosis and treatment more difficult. Through a thorough analysis of existing literature on typhoid fever, malaria, and co-infection, including research articles, case studies, and review papers, this review seeks to understand the dynamic interactions between typhoid fever and malaria co-infection. The review highlights important problems with co-infection between typhoid and malaria, such as higher morbidity and death, diagnostics-related challenges, and antibiotic resistance. Overlapping symptoms and limitations in current diagnostic tests impede accuracy. Treatment plans are made more difficult by the advent of typhoid strains that are resistant to drugs. The analysis concludes by highlighting the necessity of developing more sensitive and specific diagnostic methods in order to accurately diagnose co-infections. Going forward, the review emphasizes the need for more investigation into the immunological connections between malaria and typhoid illnesses. Essentially, this paper offers a thorough summary of the difficulties and possibilities related to co-infection between typhoid and malaria. It provides a framework for upcoming studies and initiatives that seek to improve public health and patient outcomes in the face of these intricately linked health problems.

Necroptosis is a regulated form of cell death implicated in several pathological conditions, in-cluding viral infections. In this study, we investigated the expression and correlation of necroptosis markers, MLKL, RIP1 and RIP3, in human liver tissue from fatal cases of yellow fever (YF) using immunohistochemistry (IHC). Liver samples were obtained from 21 YF-positive individuals and five flavivirus-negative controls with preserved liver parenchymal architecture. The cases un-derwent histopathological analysis, followed by tissue immunostaining with the immuno-histochemical method of streptavidin-biotin peroxidase. Using the in situ method, we evaluated the centrilobular (Z3), midzonal (Z2), periportal zone and portal tract (PT) zones of human liver parenchyma with markers for necroptosis, RIPK1, RIPK3 and MLKL. Quantitative analysis re-vealed significantly higher expression of MLKL, RIP1 and RIP3 in the liver parenchyma of YF cases compared to controls in different zones (Z3, Z2, Z1) and portal tracts (PT) of the liver, especially in zone 2. Immunostaining confirmed the localization of MLKL, RIP1 and RIP3 in hepatocytes and inflammatory infiltrates, highlighting their involvement in the pathogenesis of YF. Pearson's correlation analysis demonstrated significant correlations between necroptosis markers which indicate their coordinated regulation during YF-induced liver injury.

Infectivity assays are the key analytical technology for development of manufacturing processes for virus-based therapeutics. Here, we introduce a novel assay format that utilizes label-free bright field images to determine the kinetics of infection-dependent changes in cell morphology. In particular, cell rounding is directly proportional to the amount of infectious virus applied, enabling rapid determination of viral titers in relation to a standard curve. Our kinetic infectious virus titer (KIT) assay is stability-indicating and, due to its sensitive readout method, provides results within 24 hours post-infection. Compared to traditional infectivity assays, which depend on a single readout of an infection endpoint, cumulated analysis of kinetic data by a fit model results in precise results (CV &lt; 20%) based on only three wells per sample. This approach allows for a high throughput with ~400 samples processed by a single operator per week. We demonstrate the applicability of the KIT assay for VSV-GP and NDV, but it can potentially be extended to a wide range of viruses that induce morphological changes upon infection. The versatility of this assay, combined with its independence from specific instruments or software, makes it a promising solution to overcome the analytical bottleneck in infectivity assays within the pharmaceutical industry and as a routine method in academic research.

Zika virus (ZIKV) infection and pathogenesis are linked to the disruption of neurogenesis, congenital Zika syndrome and microcephaly by affecting neural progenitor cells. Nonstructural protein 5 (NS5) is the largest product encoded by ZIKV-RNA and is important for replication and immune evasion. Here, we studied the potential effects of NS5 on microtubules (MTs) and autophagy flux, together with the interplay of NS5 with histone deacetylase 6 (HDAC6). Fluorescence microscopy, biochemical cell-fractionation combined with the use of HDAC6 mutants, chemical inhibitors and RNA interference indicated that NS5 accumulates in nuclear structures and strongly promotes the acetylation of MTs that aberrantly reorganize in nested-like structures. Similarly, NS5 accumulates the p62 protein, an autophagic-flux marker. Therefore, NS5 alters events that are under the control of the autophagic tubulin-deacetylase HDAC6. HDAC6 appears to degrade NS5 by autophagy in a deacetylase- and BUZ domain-dependent manner and to control the cytoplasmic expression of NS5. Moreover, NS5 inhibits RNA-mediated RIG-I interferon (IFN) production, resulting in greater activity when autophagy is inhibited (i.e., effect correlated with NS5 stability). Therefore, it is conceivable that NS5 contributes to cell toxicity and pathogenesis, evading the IFN-immune response by overcoming HDAC6 functions. HDAC6 has emerged as an anti-ZIKV factor by targeting NS5.

Crimean-Congo hemorrhagic fever virus (CCHFV) is the causative agent of a tick-borne infection with significant mortality rate of up to 40% in the endemic areas, with evidence for geographical expansion. Lacking effective therapeutics and control measures, the development of protective CCHFV vaccine remains a crucial public health task. This manuscript describes, for the first time, a Bovine herpesvirus type 4 (BoHV-4) based viral vector (BoHV4-∆TK-CCHFV-N) and its immunogenicity and protection potential in BALB/c and IFNAR^-/- mice models in comparison with Adenovirus type 5 (Ad5-N) and pCDNA3.1 myc/His A (pCD-N1), two widely used vaccine platforms. All constructs expressing viral nucleocapsid (N) protein successfully elicited cytokine and total/specific antibody responses in BALB/c mice. BoHV4-∆TK-CCHFV-N and Ad5-N constructs further produced 100% protection in IFNAR^-/- mice during CCHFV Ank-2 strain lethal challenge. Despite elevated specific antibody responses in both animal models, the produced antibodies were unable to neutralize the virus in vitro. A comparison of delivery platforms was not possible, due to similar protection rates in IFNAR^-/- mice. In conclusion, vector-based CCHFV N protein expression proved to constitute an effective approach for the vaccine development pipeline and BoHV-4 emerged as a strong alternative to previously-used virus vectors.

In the intricate dance between viruses and host cells, RNA-binding proteins (RBPs) serve as crucial orchestrators of gene expression and cellular processes. We will delve into the riveting realm of viral hijacking, where viruses deftly exploit host RBPs to manipulate cellular machinery for their replication and pathogenesis. Through a masterstroke of molecular subterfuge, viruses co-opt RBPs involved in various facets of RNA metabolism - from transcription to degradation - to promote viral gene expression and evade host immune defenses. This manipulation leads to global alterations in cellular RNA metabolism, impacting essential host genes vital for immune responses and homeostasis.Unveiling this clandestine alliance between viruses and RBPs is not just a scientific pursuit, but a critical imperative for devising innovative antiviral strategies to disrupt these interactions. By unraveling the intricate interplay between viral proteins and host RBPs throughout the viral life cycle - from entry to assembly - researchers aim to identify vulnerabilities that can be targeted for therapeutic intervention. Strategies such as disrupting viral protein-RBP interactions hold promise for inhibiting viral replication and curbing pathogenesis, offering a beacon of hope in the battle against viral infections.Our manuscript elucidates the indispensable roles played by RBPs in viral replication, translation, and pathogenesis, shedding light on the molecular mechanisms driving viral success. Delving deeper, it explores how viruses intricately entwine with host RBPs, manipulating cellular signaling pathways to create a hospitable environment for viral spread. By dissecting these manipulative tactics, researchers uncover new targets for antiviral therapy, envisioning a future where tailored interventions disrupt viral-host RBP interactions with precision and efficacy.As the narrative unfolds, the therapeutic implications of targeting RBPs or their interactions with viral proteins emerge as a promising frontier in the fight against viral infections. From small molecule inhibitors to RNA-based therapeutics, innovative approaches are on the horizon, offering new avenues for combatting viral diseases. We set the stage for future research, beckoning researchers to delve deeper into the molecular intricacies of viral hijacking of RBPs and charting a course towards novel therapeutic interventions that promise to reshape the landscape of antiviral therapy.\Ultimately, it beckons the scientific community to embark on a voyage of discovery, unraveling the secrets of viral hijacking of RBPs and paving the way for transformative advances in antiviral therapeutics. The stage is set for a new chapter in the battle against viral infections, where knowledge becomes the sword and innovation the shield against the pernicious machinations of viral pathogens.

Lassa Fever is a deadly viral haemorrhagic disease, causing annually several hundreds of deaths in the Gulf of Guinea. This zoonotic disease is primarily transmitted to humans by rodents of the genus Mastomys, while secondary interhuman transmission accounts for approximately 20% of cases. Although this disease has been endemic in rural zones of the Gulf for hundreds of years, it is also characterised by epidemic outbreaks in the dry season, responsible for heavy death tolls. No licensed vaccine or satisfying treatment is currently available. Disease management is hindered by the incomplete knowledge of the epidemiology and distribution of the disease, resulting from an inadequate health and surveillance system. Additional scientific constraints such as the genetic diversity of the virus and the lack of understanding of the mechanisms of immune protection complexify the development of a vaccine. The intricate socio-economic context in the affected regions, and the lack of monetary incentive for drug development, allow the disease to persist in some of West Africa’s poorest communities. The increase in the number of reported cases and in the fatality rate, the expansion of the endemic area, as well as the threat Lassa Fever represents internationally should urge the global community to work on the disease control and prevention. The disease control requires collaborative research for medical countermeasures and tailored public health policies. Lassa Fever, created by the interconnection between animals, humans, and ecosystems, and embedded in an intricate social context, should be addressed with a ‘One Health’ approach. This article provides an overview of Lassa Fever, focusing on Nigeria, and discusses the perspectives for the control of disease.

Rift Valley fever (RVF) is a mosquito-borne zoonotic viral disease that infects both human and animals. This is a descriptive study summarizes investigation and response to RVF outbreak, using surveillance data. A RVF outbreak occurred in Berber locality in northern Sudan. We identified 246 cases of RVF including seven deaths among humans, 119 deaths and 82 abortions among Livestock. Our entomological surveillance confirmed the presence of Anopheles arabiensis, An. stephensi, Aedes aegypti, Ae. vexans, Culex pipiens, Cx. Quinquefasciatus, and Cx. theileri in the area during the outbreak. In a comparison with another outbreak of Rift Valley fever in nearby area while ago, a multisectoral One Health response strategy has resulted in strengthening the health system through re-innovating health facilities and centres and training about 200 healthcare and emergency responders. Additionally, it reduced cases and fatalities among humans by 78% and 63%, respectively, and loss in livestock due to deaths and/or abortions by 82%. The added-value of implementing One Health strategy was saving more lives and resources, while strengthening the health system. We recommend the systematic institutionalization of One Health strategy in the country as a core part of the national prevention and control strategy for zoonotic diseases epidemics and pandemics.

Herein, we examined the effects of weather parameters and individual clinicodemographic risk factors on hemorrhagic stroke (HS) incidence, severity on admission, and disability at discharge in a harsh desert climate. In a retrospective design we studied patients admitted to a stroke unit in Arab Emirates in 2016-2019. With a distributed lag nonlinear model we explored immediate and delayed effects of weather on stroke incidence. Supervised machine learning was used to build models predictive of scores in NIHSS and mRS scales. We assessed model performance by calculating ROC AUC, F1 scores, specificity, and sensitivity. HS risk increased after a significant change in any weather parameter. The risk was reduced below baseline after 1-week adjustment to environmental changes. Climate input from the previous 3 days yielded reliable classification models. Humidex was a better predictor of severity than air temperature, whereas body mass index, age, and time of day at stroke onset were the strongest clinical predictors. Weather parameters before admission were stronger predictors of disease severity than individual clinical factors. We addressed limitations of previous studies by analyzing a full set of climate parameters: ambient temperature, relative humidity, humidex, atmospheric pressure, and wind speed. Predictive models may help to optimize patient management and develop preventative strategies.

Stroke represents one of the neurological diseases most responsible for death and permanent disability in the world. Different factors, such as thrombus, emboli and atherosclerosis, take part in the intricate pathophysiology of stroke. Comprehending the molecular processes involved in this mechanism is crucial to developing new, specific and efficient treatments. Some common mechanisms are excitotoxicity and calcium overload, oxidative stress, and neuroinflammation. Furthermore, non-coding RNAs (ncRNAs) are critical in pathophysiology and recovery after cerebral ischaemia. ncRNAs, particularly microRNAs, and the long non-coding RNAs (lncRNAs) are essential for angiogenesis and neuroprotection, and they have been suggested to be therapeutic, diagnostic and prognostic tools in cerebrovascular diseases, including stroke. This review summarizes the intricate molecular mechanisms underlying ischemic and hemorrhagic stroke and delves into the function of miRNAs in the development of brain damage. Furthermore, we will analyze new perspectives on treatment based on molecular mechanisms in addition to traditional stroke therapies.

The pressure exerted on the heart and blood vessels because of blood flow is considered as an important parameter for the cardiovascular function. It determines sufficient blood perfusion as well as transportation of nutrition, oxygen and other essential factors to every organ. Pressure in the primary arteries located near the heart and the brain, known as central blood pressure (CBP), while in peripheral arteries, known as peripheral blood pressure (PBP). Normally, CBP and PBP are correlated; however, cardiovascular disorders interfere their regulation and affect the blood flow in vital organs and accessory organs, differently. Therefore, understanding each of them in normal and disease conditions is essential for managing various cardiovascular disorders and increasing their treatment outcomes. In this review, we have described the control systems (neural, hormonal, osmotic and cellular) of the blood pressure and its regulation in hypovolemic shock using centhaquine (Lyfaquin®) as a resuscitative agent.

Morphological parameters like cotton height, branches, Leaf Area Index and biomass are mainly affected by the vegetation water content (VWC). Periodical assessment of the VWC and crop parameters is required for timely management of the crop for maximizing yield. The study aimed at using both optical and microwave remotely sensed data to assess cotton crop condition based on the above mentioned traits. Vegetation indices (VI) derived from ground based measurements (5 narrow band and 2 broad band VIs) as well as satellite derived reflectance (2 broad band VIs) were assessed. Regression models were derived for estimating LAI, biomass and plant water content using the ground based indices and applied to the satellite derived spectral index (from LISS-III) map to estimate the respective parameters. HH and HV polarization from RISAT-1 were used to derive Radar Vegetation Index (RVI). The coefficient of determination of the model for estimating LAI, biomass and vegetation water content of cotton with optical vegetation index as input parameter were found to be 0.42, 0.51 and 0.52, respectively. The correlation between RVI and plant height, date of planting in terms of the age of the crop and vegetation water content were found to range between 0.4 to 0.6. The fresh biomass from RVI showed spatial variability from 100 gm-2 to 4000 gm-2 while the dry biomass map derived from NDVI showed spatial variability of 50 to 950 g m-2 for the study area. Plant water content in the district varied from 65 to 85%. The correlation between optical vegetation index and RVI was not significant. Hence a multiple linear regression model using both optical index (NDVI and LSWI) and SAR index (RVI) was developed to assess the LAI, biomass and plant water content. The model showed a R2 of 0.5 for LAI estimation but not significant for biomass and water content. This study show cased the use of combined optical and microwave (C band) remote sensing for cotton condition assessment.

To mitigate pyrethroid resistance in mosquito vectors of emerging and re-emerging human pathogens, there is an urgent need to discover insecticides with novel modes of action. Natural alternatives, such as extracts derived from plants, may serve as substitutes for traditional synthetic insecticides if they prove to be sustainable, cost-effective, and safe for non-target organisms. Hemp (Cannabis sativa) is a sustainable plant known to produce various secondary metabolites with insecticidal properties, including terpenoids and flavonoids. The goal of this study was to assess the larvicidal activity of hemp leaf extract on 1st instar mosquito larvae from both pyrethroid-susceptible (PS) and pyrethroid-resistant (PR) strains of Aedes aegypti Another goal was to identify which components of the extracts were responsible for any observed larvicidal activity. We found that methanol extract of hemp leaves induced similar concentration-dependent larvicidal activity against PS (LC50: 4.4 ppm) and PR (LC50: 4.3 ppm) strains within 48 hours. Partitioning of the dried leaf extract between methanol and revealed that full larvicidal activity was restricted to the methanol fraction. Analysis of this fraction by gas chromatography-mass spectrometry and nuclear magnetic resonance showed it to be dominated by cannabidiol (CBD). Larvicidal assays using authentic CBD confirmed this compound was primarily responsible for the toxicity of hemp leaf extract against both strains. We conclude that hemp leaf extracts and CBD have the potential to serve as viable sources for the development of novel mosquito larvicides.

Many protein expression systems are primary utilised to produce a single, specific recombinant protein. In contrast, most biological processes such as virus assembly rely upon a complex of several interacting proteins rather than the activity of a sole protein. The high complexity of the baculovirus genome, coupled with a multiphase replication cycle incorporating distinct transcriptional steps, made it the ideal system to manipulate for high-level expression of a single or co-expression of multiple foreign proteins within a single cell. We have developed and utilised a series of recombinant baculovirus systems to unravel the sequential assembly process of a complex non-enveloped model virus, Bluetongue virus (BTV). The high protein yields expressed by the baculovirus system not only facilitated structure-function analysis of each viral proteins but were also advantageous to crystallography studies and supported the first atomic level resolution of a recombinant viral protein, the major BTV capsid protein. Further, the formation of recombinant double-shelled virus-like particles (VLPs) provided insights into the structure-function relationships among the four major structural proteins of the BTV whilst also representing a potential candidate for a viral vaccine. The baculovirus multi-gene expression system facilitated the study of structurally complex viruses (both non-enveloped and enveloped viruses) and heralded in a new generation of viral vaccines.

Diarrhea and fever are prevalent childhood illnesses with potentially severe consequences, especially when they co-occur. This study investigates the prevalence and determinants of diarrhea, fever, and their coexistence among children under-five in Bangladesh. Data from the 2017-18 Bangladesh Demography and Health Survey (BDHS) were analyzed using multivariable stepwise logistic regression with backward selection. This study found that 5.0% for diarrhea, 34.0% for fever, and 3.0% for the coexistence of both illnesses. Common factors associated with childhood diarrhea and fever included the mother's education, her attitude toward wife-beating, and the child’s age (12-23 months). Diarrhea was associated with households with improved water sources and children in the Barisal division, while fever was linked to underweight children and those from more affluent backgrounds. The coexistence of both was significantly linked to underweight children, higher birth orders, and children from the Rajshahi division. Notably, child illnesses were associated with parental education, higher socio-economic status, and access to improved drinking water sources. Diarrhea affects one in 20 children, fever affects one in three, and the coexistence of both conditions affects one in 35 children in Bangladesh. The findings need further research and policy reviews to develop effective interventions and improve child health in Bangladesh.

The risk of a fatal outcome was 41% in unvaccinated patients (p = 0.713), which increased by 2.66% with co-infection with two pathogens (p = 0.342) and by 26% with three pathogens (p = 0.005). Additionally, 50% of ICU patients had a triple infection, compared with only 1.3% in the inpatient unit (p = 0.0029). The risk of death and/or ICU admission was 12 times higher (p = 0.042) with an additional pathogen and increased by 95% (p = 0.003) with a third concomitant pathogen. Regular multiplex testing is important for prompt treatment and targeted antibiotic use.

Commercially cultivated Prunus species are commonly grown in adjacent or mixed orchards, and can be infected with unique or commonly shared viruses. Apple (Malus domestica), another member of the Rosacea and distantly related to Prunus, can share the same growing regions and common pathogens. Pollen can be a major route for virus transmission, and analysis of the pollen virome in tree fruit orchards can provide insights into these virus pathogen complexes from mixed production sites. Commercial honey bee (Apis mellifera) pollination is essential for improved fruit set and yield in tree fruit production systems. Here we describe the metagenomics-based detection of plant viruses through bee and pollen samples collected during the spring bloom period from a mixed Prunus and Malus orchard. Twenty-one unique viruses were detected in samples collected during apricot (Prunus armeniaca), sweet cherry (Prunus avium), peach (Prunus persica), and apple blooms. Ilarviruses prune dwarf virus (PDV) and prunus necrotic ringspot virus (PNRSV), Secoviridae family members tomato necrotic ringspot virus, tobacco necrotic ringspot virus, and prunus virus F, and Capillovirus cherry virus A (CVA) were detected in all time points, while other viruses were detected with restricted ranges. These results demonstrate the benefits of area-wide monitoring through bee pollination activities, and provide new insights into the diversity of viruses in tree fruit pollination ecosystems.

Long COVID (Post-Acute Sequelae of COVID-19, PASC) is a consequence of infection by SARS-CoV-2 that continues to disrupt the well-being of millions of affected individuals for many months beyond their first infection. While the exact mechanisms underlying PASC remain to be defined, hypotheses regarding the pathogenesis of Long COVID are varied and include (but are not limited to) dysregulated local or systemic inflammatory responses, autoimmune mechanisms, viral-induced hormonal imbalances and long-term persistence of virus and/or fragments of viral RNA or proteins. This review article is based on a comprehensive review of the wide range of symptoms most often observed in long COVID and an attempt to integrate that information into a plausible hypothesis for the pathogenesis of PASC. In particular, it is proposed that longterm dysregulation of the gut in response to viral persistence could lead to the myriad of symptoms observed in PASC.

Little is known about how individual virus lineages replicating during acute Human Immunodeficiency Virus or Simian Immunodeficiency Virus (HIV/SIV) infection persist into chronic infection. In this study, we use molecularly barcoded SIV (SIVmac239M) to track distinct viral lineages for 12 weeks after intravenous and intrarectal challenge in macaques. Two Mafa-A1*063+ cynomolgus macaques (Macaca fascicularis) were challenged intravenously (IV), and two Mamu-A1*001+ rhesus macaques (Macaca mulatta) were challenged intrarectally (IR) with 200,000 Infectious Units (IU) of SIVmac239M. We deep sequenced the molecular barcode from all animals over 12 weeks to characterize the diversity and persistence of virus lineages, as well as the sequences of T cell epitopes during acute SIV infection. During the first three weeks post-infection, we found ~175-950 times more unique virus lineages circulating in the animals challenged intravenously than those challenged intrarectally, suggesting that challenge route is the primary driver restricting the transmission of individual viral lineages. Additionally, the emergence of escape variants can occur on multiple virus templates simultaneously, but elimination of some templates is likely a consequence of additional host factors. These data imply that virus lineages present during acute infection can be eliminated from the virus population even after initial T cell selection.

Food-borne transmission is a recognized route for many viruses associated with gastrointestinal, hepatic or neurological diseases. Therefore, it is essential to identify new bioactive compounds with broad-spectrum antiviral activity is needed to exploit innovative solutions against these hazards. Lately, antimicrobial peptides (AMPs) have been recognized as promising antiviral agents. Indeed, while the antibacterial and antifungal effects of these molecules have been widely reported, their use as potential antiviral agents has not yet been fully investigated. Herein, the antiviral activity of previously identified or newly designed AMPs, was evaluated against the non-enveloped RNA viruses, Hepatitis A virus (HAV), and Murine Norovirus (MNV), a surrogate for human Norovirus. Moreover, specific assays were performed to recognize at which stage of the viral infection cycle the peptides could function. Results showed that almost all peptides displayed virucidal effects with about 90% of infectivity reduction on HAV or MNV. However, the decapeptide RiLK1 demonstrated, together with its antibacterial and antifungal properties, a notable reduction in viral infection for both HAV and MNV, possibly through direct interaction with viral particles or inhibition of the viral bonding to the cell receptors. Hence, RiLK1 could represent a versatile ‘antimicrobial agent effective against various foodborne pathogens including viruses, bacteria, and fungi.

Wastewater-Based Epidemiology (WBE) is currently used to monitor not only the spread of the pandemic virus SARS-CoV-2 but also for other viruses in endemic conditions, particularly in the absence of syndromic surveillance. Continuous monitoring of sewage requires high costs and significant time investment, highlighting the need for standardized methods and structured monitoring strategies. In this context, we conducted weekly wastewater monitoring in northwestern Italy, targeting Human Adenovirus (HAdV), Norovirus Genogroup II (NoVggII), Enterovirus (EV), and SARS-CoV-2. Samples collected at the entrance of treatment plants were concentrated using PEG/NaCl precipitation and viral nucleic acids were extracted and detected by real-time (RT-)qPCR. NoVggII resulted the most identified target (84.4%), followed by HAdV, SARS-CoV-2, and EV. Only HAdV and EV exhibited seasonal peaks in spring and summer. SARS-CoV-2 results compared with data previously collected in the same study area (February 2021 to September 2021) revealed a shift from an epidemic to a pandemic status, likely due to the evolution of variants. In conclusion, WBE, using standardized methods and an efficient monitoring strategy, proves valuable for virus surveillance in pandemic and epidemic scenarios, enabling the identification of temporal-local distribution patterns that are useful for making informed public health decision.

This review seeks to explain four features of viral respiratory illnesses that have perplexed generations of virologists: (1) the seasonal timing of respiratory illness; (2) the common viruses causing respiratory illness worldwide, including year-round disease in the Tropics; (3) the rapid response of outbreaks to weather, specifically temperature; (4) the rapid arrival and termination of epidemics caused by influenza and other viruses. The inadequacy of the popular explanations of seasonality is discussed, and a simple hypothesis is proposed, called Temperature Dependent Viral Tropism (TDVT), that is compatible with the above features of respiratory illness. TDVT notes that viruses can transmit themselves more effectively if they moderate their pathogenicity (thereby maintaining host mobility) and suggests that endemic respiratory viruses accomplish this by developing thermal sensitivity within a range that supports organ-specific viral tropism within the human body, whereby they replicate most rapidly at temperatures below body temperature. This allows them to confine themselves to the upper respiratory tract and to avoid infecting the lungs, heart, gut etc. Biochemical and tissue-culture studies show that “wild” respiratory viruses show such natural thermal sensitivity. The typical early autumn surge of colds and the existence of respiratory illness in the Tropics year-round at intermediate levels are explained by the tendency for strains to adapt their thermal sensitivity to their local climate and season. The TDVT hypothesis has important practical implications for preventing and treating respiratory illness including Covid-19. TVDT is testable with many options for experiments to increase our understanding of viral seasonality and pathogenicity.

Dengue virus an arbovirus is endemic in an area that comprise almost half of the world's population, contrary to past beliefs that dengue virus differentiate from other neuroinvasive arbovirus due to its lack of neurological invasion and disease related neurological complications excluding hemorrhagic and thromboembolic , the body of evidence have grown to demonstrate a series of neurological manifestations linked to dengue virus with possible mechanisms involving direct virus invasion of the nervous system or immune mediated complications. In this review we provide a wide approach to this neglect but not so rare manifestations of a very common disease.

Background: Pharmacists need up-to-date knowledge and decision-making support in HIV care. We aim to develop MARVIN-Pharma, an adapted artificial intelligence-based chatbot initially for people with HIV, to assist pharmacists, considering evidence-based needs. Methods: From Dec 2022 to Dec 2023, an online needs-assessment survey evaluated Québec pharmacists' knowledge, attitudes, involvement, and barriers relative to HIV care, alongside perceptions relevant to the usability of MARVIN-Pharma. Recruitment involved convenience and snowball sampling, targeting National HIV and Hepatitis Mentoring Program affiliates. Results: Forty-one pharmacists (28 community, 13 hospital-based) across 15 Québec municipalities participated. Participants perceived their HIV knowledge as moderate (M=3.74/6). They held largely favorable attitudes towards providing HIV care (M=4.02/6). They reported a “little” involvement in the delivery of HIV care services (M=2.08/5), most often ART adherence counseling, refilling, and monitoring. The most common barriers reported to HIV care delivery were a lack of time, staff resources, clinical tools, and HIV information/training, with pharmacists at least somewhat agreeing that they experienced each (M≥4.00/6). On average, MARVIN-Pharma's acceptability and compatibility were in the ‘undecided’ range (M=4.34, M=4.13/7, respectively), while pharmacists agreed to their self-efficacy to use online health services (M=5.6/7). Conclusion: MARVIN-Pharma might help address pharmacists' knowledge gaps and barriers to HIV treatment and care, but pharmacist engagement in the chatbot’s development seems vital for its future uptake and usability.

Both bacteria product flagellin and macrophages are implicated in HIV infection/disease progression. However, the impact of their interaction on HIV infection and the associated mechanisms remain to be determined. We thus examined the effect of the flagellins on HIV infection of primary human macrophages. We observed that the pretreatment of macrophages with the flagellins from the different bacteria significantly inhibited HIV infection. The mechanistic investigation showed that the flagellin treatment of macrophages downregulated the major HIV entry receptors (CD4 and CCR5) and upregulated the CC chemokines (MIP-1α, MIP-1β, and RANTES), the ligands of CCR5. These effects of the flagellin could be compromised by a toll like receptor 5 (TLR5) antagonist. Given the important role of flagellin as a vaccine adjuvant in TLR5 activation-mediated immune regulation and in HIV infection of macrophages, future investigations are necessary to determine the in vivo impact of flagellin-TLR5 interaction on macrophage-mediated innate immunity against HIV infection and the effectiveness of flagellin adjuvant-based vaccines studies.

In mesoscale eddies, chemical properties and biological composition are different from those in surrounding water, due to their unique physical processes. It is unclear how physical-biological coupling occurs in warm-core eddies, particularly since no study has examined the relationship between bacteria and viruses. The purpose of the present study was to examine the influence of anticyclonic warm eddy on the relationship between bacterial and viral abundances as well as viral activity (viral production) in different depths. In the core of warm eddy, bacterial abundance (0.48 to 2.82 ×105 cells mL−1) fluctuated less than that of the outside eddy (1.12 to 7.03×105 cells mL−1). In particular, there was four-folds higher of viral-bacterial abundance ratio (VBR) estimated within the eddy below DCM than the outside eddy. We suggest that prevailing physical forces with downwelling at the center of the anticyclonic warm eddy, viruses can also be transmitted into the deep ocean directly through adsorption on particulate organic matter during sinking. Overall, our findings provide valuable insights into the interaction between bacterial and viral communities and their ecological mechanism within the warm eddy.

Pregnant women (PW) are at a higher risk of diseases and hospitalization from viral respiratory infections, specially influenza, due to cardiopulmonary and immunological changes. This study assessed the impact of viral respiratory infections on PW hospitalized with severe acute respiratory infection (SARI). It´s a cross-sectional study with 42 PW and 85 non-pregnant women (NPW) admitted with SARI to two tertiary hospital between January 2015 and December 2019. The rate of virus prevalence, SARI hospitalization, length of hospital stay, oxygen supplementation, intensive care unit (ICU) admission, and death were comparable between PW and NPW. Multivariate analysis showed that PW had a higher rate of viral SARI hospitalizations (OR = 2.37; 95% CI =1.02 - 5.48) compared to NPW, with influenza virus being the most prevalent (aOR =7.58; 95% CI =1.53 - 37.66). Length of hospital stay (aOR = 0.83; 95% CI = 0.73 – 0.95) and admission to the ICU (aOR=0.028; 95% CI=0.004 - 0.25) were lower in PW compared to hospitalized NPW. Respiratory viruses had a greater impact on the frequency of SARI in the group of PW. Although PW had a higher rate of influenza SARI, they had a better outcome than NPW due to the treatment they received.

African swine fever virus (ASFV), a highly contagious pathogen characterized by a complex structure and a variety of immunosuppression proteins, causes hemorrhagic, acute, and aggressive infectious disease that severely injure the pork product and industry. However, there is no effective vaccine or treatment. The main reasons are not only the complex mechanisms that lead to immunosuppression, but also the unknown functions of various proteins. This review summarizes the interaction between ASFV and host immune system, along with the involvement of virulence related genes and proteins, as well as the corresponding molecular mechanism of immunosuppression of ASFV, encompassing pathways such as cGAS-STING, NF-κB, JAK/STAT, apoptosis, and other modulation. The aim is to summarize the dynamic process during the ASFV infection and entry into host cell, provide a rational insight into development of vaccine and a better clear knowledge of how ASFV impacts host.

Background: The SARS-CoV-2 laboratory PCR tests were generally reported only as binary positive or negative outcomes. Instead test positivity, these results contain a great deal of epidemiological information related to viral transmission patterns in populations. These transmission patterns during India’s SARS-CoV-2 viral waves remain largely undocumented. Methods: We analysed 2.7 million real-time polymerase chain reaction (PCR) testing records collected in Mumbai, a bellwether for other Indian cities. We used the inverse of cycle threshold (Ct) values to determine community-level viral load. We quantified wave-specific differences by age, sex and slum population density. Results: Overall PCR positivity was 3.4% during non-outbreak periods, rising to 23.2% and 42.8% during the Aleph (June-November 2020) and Omicron waves (January 2022), respectively, but only 9.9% during the Delta wave (March-June 2021). The community-level median Ct values fell and rose ~7-14 days prior to PCR positivity rates. Viral loads were 4-fold higher during the Delta and Omicron waves than during non-outbreak months. The Delta wave had high viral loads at older ages, in women and in areas of higher slum density. During the Omicron wave, differences in viral load by sex and for slum density had disappeared, but older adults continued to show higher viral load. Conclusions: Mumbai’s viral waves had markedly high viral loads representing an early signal of pandemic trajectory. Continue the vaccination in elderly Indians could reduce viral load in subsequent waves. Ct values are practicable monitoring tools.

Fermented foods have long been known to have immunomodulatory capabilities and fermentates derived from the lactic acid bacteria of dairy products can modulate the immune system. We have used skimmed milk powder to generate novel fermentates using Lb. helveticus strains SC234 and SC232 and we demonstrate here that these fermentates can enhance key immune mechanisms that are critical to the immune response to viruses. We show that our novel fermentates SC234 and SC232 can positively impact on cytokine and chemokine secretion, nitric oxide (NO) production, cell surface marker expression, and phagocytosis in macrophage models. We demonstrate that fermentates SC234 and SC232 increase the secretion of cytokines IL-1β, IL-6, TNF-α, IL-27, and IL-10, promote an M1 proinflammatory phenotype for viral immunity via NO induction, decreases chemokine expression of Monocyte Chemoattractant Protein (MCP), increasing cell surface marker expression, and enhance phagocytosis in comparison to their starting material. These data suggest that these novel fermentates have potential as novel functional food ingredients for the treatment, management and control of viral infection.

Viral co-infections, where a host is infected by multiple viruses simultaneously, are common in the human population. Human viral co-infections can lead to complex interactions between viruses and the host immune system, affecting the clinical outcome and posing challenges for treatment. Understanding the types, mechanisms, impacts, and identification methods of human viral co-infections is crucial for the prevention and control of viral diseases. In this review, we first introduce the significance of studying human viral co-infections and summarize the current research progress and gaps in this field. We then classify human viral co-infections into four types based on the pathogenic properties and species of the viruses involved. Next, we discuss the molecular mechanisms of viral co-infections, focusing on virus-virus interactions, host immune responses, and clinical manifestations. We also summarize the experimental and computational methods for identifying viral co-infections, emphasizing the latest advances in high-throughput sequencing and bioinformatics approaches. Finally, we highlight the challenges and future directions in human viral co-infection research, aiming to provide new insights and strategies for the prevention, control, diagnosis, and treatment of viral diseases. This review provides a comprehensive overview of the current knowledge and future perspectives on human viral co-infections, and underscores the need for interdisciplinary collaborations to address this complex and important topic.

Familial Mediterranean fever (FMF) is a systemic autoinflammatory disorder caused by inherited mutations in the MEFV (Mediterranean FeVer) gene located on chromosome 16 (16p13.3) and coding pyrin protein. Despite the existing data on MEFV mutations, the exact mechanism of their effect on the development of pathological processes leading to autoinflammation observed in FMF, remains unclear. Induced pluripotent stem cells (iPSCs) are considered an important tool for studying the molecular genetic mechanisms of various diseases due to their ability to differentiate into any cell type, including macrophages, which contribute to the development of FMF. In this study, we developed iPSCs of an Armenian patient with FMF having M694V, p.(Met694Val) (c.2080A&gt;G, rs61752717) pathogenic mutation in exon 10 of the MEFV gene. As a result of direct differentiation, macrophages expressing CD14 and CD45 surface markers were obtained. In addition, we found that the morphology of patient macrophages derived from iPSCs with MEFV mutation was significantly different from that of differentiated from iPSCs of a healthy donor carrying wild-type MEFV gene.

The risk of the emergence and reemergence of zoonoses is high in regions that are under anthropogenic actions, as they contribute to the risk of vector disease transmission. Yellow fever (YF) is among the main pathogenic arboviral disease in the world, and the Culicidae Aedes albopictus has been proposed to have the potential to transmit yellow fever virus (YFV). This mosquito inhabits both urban and wild environments, and under experimental conditions, it has been shown to be susceptible to infection by YFV. In this study, the vector competence of the mosquito Ae. albopictus for the YFV was investigated. Female Ae. albopictus were exposed to non-human primates (NHP) of the genus Callithrix infected with YFV for blood meal. Subsequently, on the 14th and 21st days post infection, the legs, heads, thorax/abdomen and saliva of the arthropods were collected and analyzed by viral isolation and molecular analysis techniques to verify the infection, dissemination and transmission. The presence of YFV was detected in saliva samples through viral isolation and in the head, thorax/abdomen and legs both by viral isolation and by molecular detection. The susceptibility of Ae. Albopictus to YFV confers a potential risk of reemergence of urban YF in Brazil.

Based on the Flashing Ratchet Potential (FRP) and Electro-Spectroscopy detection techniques, a new detection method was experimentally examined. This method allows the detection of sub-micro particles in the human exhaled air such as viral particles and other biological agents. The detection signal created by this method is carried out by electron current buildup forming an Electric Current-Spectrum (ECS) distinguishing the contents of the exhaled air samples. The detection method was developed based on FRP and a beam of free charges passing through the electrodes of the FRP. The ECS is characterized by low-energy free charges interacting with the medium through which they pass, where numerous free charges are scattered (delayed) as a result of these interactions. The resulting ECS is characterized by FRP's capacity to drift back the delayed free charges to their original starting positions. By comparing the ECS of two exhale air samples, this new technology can be utilized to identify the presence of viral and microorganisms’ particles. The time-escalating ECS difference quickly indicates the presence of such particles. Moreover, the FRP's optimal operating settings was experimentally defined, in addition to the experimental evaluation of its functionality to confirm the FRP's promising sensing capabilities, which were statistically examined several times to ensure the reproducibility of the results.

Lumpy skin disease (LSD), caused by a virus within the Poxviridae family and Capripoxvirus genus, induces nodular skin lesions in cattle, spreading through direct contact and insect vectors, significantly affecting global cattle farming. Despite available vaccines, their effectiveness is limited by poor bioavailability and adverse effects. Our study aimed to identify potential inhibitors targeting LSD-associated DNA polymerase protein, selecting LSDV039 for further investigation through comprehensive analysis and computational methods. Virtual screening revealed rhein and taxifolin as potent binders among 380 phytocompounds, with respective affinities of -8.965 and -7.195 kcal/mol. Canagliflozin and tepotinib exhibited strong affinities (-9.858 and -8.856 kcal/mol) among 718 FDA-approved antiviral drugs. Molecular dynamics simulations of canagliflozin, tepotinib, rhein, and taxifolin highlighted taxifolin's superior stability and binding energy. Rhein displayed compactness in RMSD and RMSF but fluctuations in Rg and SASA, while canagliflozin demonstrated stability compared to tepotinib. The study highlights the promising potential of repurposed drugs and phytocompounds as LSD therapeutics. However, extensive validation through in-vitro, in-vivo, and clinical trials is crucial for their practical application.

Lassa fever, commonly known as Lassa hemorrhagic fever (LHF), is one of the progressive illnesses invading a large population of two to three million individuals in West Africa. The infection transmitted through the rodents severely impacts the local population and the medical professionals in surrounding areas, which were also the primary target of LHF. In epidemic areas, Lassa fever causes a public health threat since it poses a significant morbidity and fatality Case rate (CFR) ≥ 50%). The disease is widespread in West Africa and has developed into one of the most common and life-threatening viral hemorrhagic fevers. Monitoring and preventing persistent disease outbreaks has been challenging in affected regions due to insufficient healthcare facilities, diagnostics labs, care centers, and low socioeconomic conditions. An absence of public awareness and the emergence of an ecological niche is advantageous for the survival and multiplication of the mouse (Mastomys natalensis) inhabiting the Lassa virus serving as the disease's natural host and reservoir. The current review focuses on early diagnosis and appropriate treatment, highlighting the immediate requirement of clinically approved vaccines for LHF, causing preventative and control actions more difficult in the present era.

Introduction: Dengue is a mosquito transmitted arboviral infection. In dengue fever spontaneous bleeding in different parts of body occurs; but spontaneous bleeding into rectus muscle leading to haematoma formation is rare. Case Presentation: A 72-year-old hypertensive female presented with high grade intermittent fever with chills and rigors for last four days. She was diagnosed to have dengue fever (NS1Ag -Reactive) on the day before admission. At admission, on examination she was found to be have dehydration. Immediately she was put on IV fluids, antiemetics and other supportive therapy. At admission she had low platelets, low haemoglobin, total leucocyte counts, with raised liver enzymes. On day 3 of illness, she had significant drop of haematocrit with low blood pressure and subsequently she managed with packed red blood cell (PRBC) transfusion. But on 9th day of illness, she has severe right iliac fossa pain mimicking acute appendicitis. CECT of abdomen showed soft tissue lesion in right lower abdomen (Inflammatory/ hematoma along rectus sheath) which was managed conservatively as per surgical opinion. 10 days past discharge she had no pain in right iliac fossa and size of hematoma was significantly reduced. Discussion: In dengue fever, hematoma can be formed any vulnerable part in the but there are only a few cases reported to be having rectus sheath hematoma. Rectus sheath hematoma (RSH) has been mistaken for many acute abdominal diseases like- acute appendicitis. Our case mimicked acute appendicitis and managed conservatively with IV fluids, analgesics, Blood transfusion as it fits into RSH type II. Conclusion: It is important to be vigilant in the patients who presents with abdominal pain in severe dengue cases. Prompt imaging in relevant areas could make the diagnosis and father treatment possible.

Rapid progress in gene editing based on clustered regularly interspaced short palindromic repeats/CRISPR-associated protein (CRISPR/Cas) has revolutionized the study of gene and genome function and genetic disease correction. While numerous genetically modified cellular and animal models have been created to understand biological processes, the clinical application of CRISPR/Cas tools has been impeded by off-targeting and delivery problems. It is generally accepted that the delivery of CRISPR in the form of a ribonucleoprotein complex (RNP) substantially reduces the time of DNA exposure to the effector nuclease, minimizing off-target effects and facilitating clinical usage. This review focuses on CRISPR/Cas RNP delivery with retro/lentiviral particles and exosomes, whose parallel production by cells transfected with viral vectors is underestimated. We critically evaluate specific mechanisms of extracellular particle formation and loading with CRISPR/Cas for each system. Additionally, the details of Cas-nanoparticle entry and uncoating, previously unappreciated in the context of gene editing efficiency, are discussed. Based on existing knowledge about the consequences of intervention in retroviral assembly, entry, or exosome formation, we outline the potential problems with CRISPR/Cas delivery using extracellular nanoparticles and ways to address them.

Every year, General Practitioners (GPs) see over 13 million patients for dermatological concerns making dermatology the highest referring speciality. Artificial Intelligence (AI) systems could improve system efficiency by supporting clinicians in making appropriate referrals, but they are, like human clinicians, imperfect and there may be a trade-off between sensitivity and specificity that is likely to result in false negatives. In this paper, a study is presented to explore two areas. Firstly, the aptitude of GPs to trust appropriately (or not trust) the outputs of a fictitious AI-based decision support tool when assessing skin lesions. Secondly, to identify which individual characteristics could make GPs less prone to adhere to erroneous diagnostics results and to refrain from passive adherence to AI. Findings suggest that when the AI is correct, there is a positive effect on GPs’ performance and confidence suggesting the potential to reduce referrals for benign lesions. However, when an inexperienced GP is presented with a false-negative result, they may passively deviate from their initial clinical judgement to accept the wrong diagnosis provided. AI systems will have a false-negative rate and, when adopting new technologies, this needs to be acknowledged and fed into risk-benefit discussions and considerations around additional safety measures.

Viral variant analysis is a bedrock of the disease surveillance. When combined with temporospatial analysis variant analysis can further the knowledge of disease spread in a study area. This paper suggests a method to perform the analysis in an operational setting which will allow for real-time surveillance of viral variants and allow local public health professionals to rapidly respond to changes in the evolution of the disease. This method includes three main subprocesses: preprocessing, analysis, and rendering. This method can be performed across multiple software platforms. A use case is given in which it was found that this method helped a hospital system understand the spread of SARS-CoV-2 in Northeast, Ohio.

Chronic myelomonocytic leukemia (CMML) is a hematological neoplasm characterized by monocytosis, splenomegaly, thrombocytopenia and anemia. Moreover, it is associ-ated with SRSF2 mutations and rarely with CSF3R variants. The presented case is an 84-year-old patient with persistent anemia and monocytosis. Due to the presence of dysmorphic granulocytes, monocyte atypia and myeloid precursors in peripheral blood, the patient was submitted to bone marrow examination. The diagnosis was consistent with CMML type 2. Hemocoagulative test showed an increase of fibrinolysis markers. Next generation targeted sequencing showed TET2 and SRSF2 mutations, along with an unexpected CSF3R germline missense variant, rarely encountered in CMML. The pa-tient started Azacitidine treatment reaching normal hemostatic process values. In con-clusion, we identified a heterozygous germline mutation that, cooperating with TET2 and SRSF2 variants, have been responsible for the hemorrhagic manifestation.

Begomoviruses, which belong to the Geminiviridae family, are intracellular parasites transmitted by whiteflies to dicotyledonous plants, significantly damaging agronomically relevant crops. These nucleus-replicating DNA viruses need to move intracellularly from the nucleus to the cytoplasm and then, like other plant viruses, spread systemically throughout the plant to cause dis-ease. The transport proteins of begomoviruses play a crucial role in recruiting host components for the movement of viral DNA within and between cells while exhibiting functions that suppress the host's immune defense. Pioneering studies on species of the Begomovirus genus have identified specific viral transport proteins involved in intracellular transport, cell-to-cell movement, and systemic spread. Recent research has primarily focused on viral movement proteins and their interaction with the cellular host transport machinery, significantly expanding our understanding of viral infection pathways. This review focuses on three main aspects: (i) the role of viral transport proteins, specifically movement proteins (MPs) and nuclear shuttle proteins (NSPs), (ii) their ability to recruit host factors for intra- and intercellular viral movement, and (iii) suppress antiviral immunity, with a particular emphasis on bipartite begomoviral movement proteins.

African swine fever has damaged the foundation of China’s hog industry, caused a serious decline in hog production, highlighted the contradiction between supply and demand in the pork market, and led to major economic and social impacts. This study measured the industrial resilience of 31 Chinese provinces which faced the African swine fever shock and its spatial and temporal differentiation characteristics from 2018-2021 in terms of the two dimensions of resistance and recoverability. Using Geodetector, the study explored the key factors influencing the resilience of China’s hog industry. The results showed that 2018-2019 and 2020-2021 were the resistance and recovery periods of the hog industry under the African swine fever shock, respectively, with poor resilience characterizing the resistance period and improved resilience exemplifying the recovery period. At the early stage of the African swine fever outbreak, Tianjin, Shanxi, Guangxi and Yunnan had robust resistance in the hog industry, and the slaughter rate, economic level, mortality rate, carcass weight and culling rate showed the highest explanation for the resistance. At the most severe stage of the outbreak, the resistance of the hog industry in all provinces was generally poor, and the slaughter rate, per capita consumption and scale level showed the highest explanation for the resistance. In the period of rapid recovery of hog production, the recoverability of each province was very strong, and the industrial structure, culling rate, economic level and resource carrying capacity showed the highest explanation for the recoverability. In the reasonable adjustment period of hog production capacity, the recoverability based on the breeding sow inventory in 13 provinces, including Henan, Shandong and other large hog breeding provinces, was negative, and the scale level, slaughter rate, per capita consumption and resource carrying showed the highest explanation for the recoverability. It is recommended to take measures to enhance the resilience of the hog industry, strengthen the prevention and control of hog epidemics, improve the monitoring and early warning mechanism, and strive to enhance the ability of the hog industry to cope with major animal epidemics.

African swine fever (ASF) is a notifiable viral disease of domestic and wild suids. Despite intensive re-search efforts, the pathogenesis of the disease is still far from being understood. Analysis of biomarkers in different body fluids may supplement traditional pathogenesis studies. As reliable protocols are often es-tablished in laboratories with lower biosafety, reliable inactivation of samples is crucial. The objective of this study was to find a procedure that inactivates the virus while preserving the biomarkers for down-stream analyses. To this means, three different inactivation protocols were employed, namely Tergitol-type NP-40 (NP-40) and polyoxyethylene-p-t-octylphenol (Triton X-100), respectively, and one with 95 °C heating. It could be demonstrated that all samples treated with 0.5% (v/v) concentration of both deter-gents showed absence of virus infectivity. The same was true for heated samples. However, heated serum was not suitable for analyses. Next, the treatment impact on biomarker readouts was assessed. While all protocols had an impact on the detection of biomarkers, correlation was retained. Especially NP-40 could be the desired detergent for more accurate measurements while achieving efficient virus inactivation. Based on these studies, samples can be reliably inactivated for most biomarker analyses and thus broader interdisciplinary cooperation is possible.

Three decades have now passed since the first papers linking climate change to issues in human disease and healthcare. One of the most active topics in this area has been the implication of climate change events, particularly temperature and humidity fluctuations, in the northward spread of vector-borne viruses from more tropical regions into Europe and North America. However, some detailed studies of one such emerging disease, tick-borne encephalitis virus (TBEv), have called the connection into question, concentrating the debate on the investigation of precise mechanisms for the spread of viral disease. More recently, firmer statistical correlations have been made between climate variables, the presence of insect vectors and the prevalence of viral disease, particularly for West Nile Virus (WNV). These insights suggest avenues for mechanistic confirmation of the involvement of climate change in other diseases where the connection remains conjectural.

The success of many viruses depends upon cooperative interactions between viral genomes. For example, viruses that coinfect the same cell can share essential gene products, such as replicase, the enzyme that replicates the viral genome. However, when cooperation occurs, there is the potential for ‘cheats’ to exploit that cooperation. We suggest that: (1) the biology of viruses makes viral cooperation particularly susceptible to cheating; (2) cheats are common across a wide range of viruses, including viral entities that are already well studied, such as defective interfering genomes, and satellite viruses. Consequently, evolutionary theory developed to explain cheating offers a conceptual framework for understanding and manipulating viral dynamics. At the same time, viruses offer unique opportunities to study how cheats evolve, because cheating is relatively common in viruses, compared with taxa where cooperation is more usually studied, such as animals.

Abstract: Background: Viral hepatitis B and C (HBV and HCV) pose significant public health challenges globally, particularly in Nigeria, where access to healthcare and treatment affordability are major concerns. This study aims to identify sociodemographic and clinical predictors of health insurance coverage among patients with HBV and HCV in Nigeria. Methods: A cross-sectional facility-based study was conducted at two secondary hospitals in Nasarawa State, Nigeria. Par-ticipants included patients diagnosed with HBV, HCV, or both and are > 18 years old. Data were collected using a structured questionnaire covering sociodemographic and clinical information, health insurance details, and economic impact. Logistic multivariate regression analysis was used to analyze the relationship between sociodemographic/clinical variables and health insurance status. Results: Out of 295 participants included in the final analysis, 67.1% had health insur-ance, primarily covering hepatitis screening and vaccination. Being aged 31-45 years (adjusted Odds Ratio [aOR]: 5.72, 95% Confidence Interval [CI]: 1.4 - 23.28, p = 0.02), having post-secondary education (aOR: 11.73, CI: 4.09 - 33.66, p < 0.001), and being HIV-positive (aOR: 2.86, CI: 1.02 - 8.02, p = 0.046) were significant predictors of health insurance coverage. Being unemployed significantly reduced the likelihood of having health insurance (aOR: 0.04, CI: 0.01 - 0.11, p < 0.001).Conclusions: This study reveals high insurance coverage among patients seeking viral hepatitis services in Nasarawa state, Nigeria and provides critical insights into the sociodemo-graphic predictors of health insurance coverage. It also highlights the need for the expansion health insurance benefit package that covers for viral hepatitis diagnosis and treatment, espe-cially for the younger adults, unemployed and less educated populations. This should be followed with adequate budgeting and policy implementation monitoring efforts, which are crucial for Nigeria's journey towards universal health coverage and elimination of viral hepatitis.

Background: Uncontrolled hemorrhage is a major preventable cause of death in patients with trauma. However, the majority of large animal models of hemorrhage have utilized controlled hemorrhage rather than uncontrolled hemorrhage to investigate the impact of immunopathy and coagulopathy on multi-organ failure (MOF) and mortality. This study evaluates these alterations in a severe porcine-controlled and uncontrolled hemorrhagic shock (HS) model. Methods: Anesthetized female swine underwent controlled hemorrhage (22 ml/kg) and uncontrolled hemorrhage by partial splenic resection followed with or without lactated Ringer solution (LR) or Voluven® resuscitation. Blood chemistry, physiologic variables, systemic and tissue levels of complement proteins and cytokines, coagulation parameters, organ function, and damage were recorded and assessed. Results: HS resulted in systemic and local complement activation, cytokine release, metabolic acidosis, hyperkalemia, MOF, and no animal survival. Resuscitation with LR and Voluven® after HS improved hemodynamic parameters (MAP and SI), metabolic acidosis, hyperkalemia, and survival but resulted in increased complement activation and worse coagulopathy. Compared with the LR group, the HS animal treated with Voluven® had worse dilutional anemia, coagulopathy, renal and hepatic dysfunction, increased myocardial complement activation and renal damage, and decreased survival rate. Conclusions: Hemorrhagic shock triggers early immunopathy and coagulopathy that appear associated with MOF and death. This study indicates that immunopathy and coagulopathy are therapeutic targets that may be addressed with a high-impact adjunctive treatment to conventional resuscitation.

It was the aim of this study to examine whether the usage of the vaccine COXEVAC® (Ceva Santé Animale) could reduce the consumption of antibiotics in Q-fever-positive dairy farms. Additionally, the effects of other herd-level factors on the consumption of antibiotics were investigated. In this longitudinal cohort study, 36 farms with vaccination and 13 farms without vaccination participated. In all herds, Coxiella burnetii had been directly or indirectly diagnosed. To compare the treatment frequency of antibiotics between the vaccinated group and the non-vaccinated group, the consumption of antibiotics for each farm was collected using the veterinary documents about the application and delivery of antibiotics. To gather detailed information about herd data, nutrition, milking management, housing, and animal health, the farmers were interviewed with the help of a questionnaire. The results suggest that there might be an association between the vaccination against Q fever and a reduced consumption of antibiotics. Neither herd size nor milk yield level influenced the consumption of antibiotics in the study herds. Type of flooring and udder cluster disinfection while milking were associated with a lower and higher therapy frequency, respectively. Further studies are necessary to elucidate the cause-effect relationship between vaccination and the consumption of antibiotics.

Chikungunya virus (CHIKV) is a mosquito borne RNA virus that poses an emerging threat to humans. As other RNA viruses, CHIKV encodes an error-prone RNA polymerase which, in addition to full-length genomes, gives rise to truncated, non-functional genomes coined defective viral genomes (DVGs). DVGs have been intensively studied in the context of therapy, as they can inhibit viral replication and dissemination in their hosts. In this work, we interrogate the influence of viral RNA secondary structures on the production of CHIKV DVGs. We experimentally map RNA secondary structures of CHIKV genome using selective 2′-hydroxyl acylation analyzed by primer extension and mutational profiling (SHAPE-MaP), which couples chemical labelling with next-generation sequencing. We correlate the inferred secondary structure with preferred deletion sites of CHIKV DVGs. We document an increased probability of DVG generation with truncations at unpaired nucleotides within the secondary structure. We then generated a CHIKV mutant bearing synonymous changes at the nucleotide level to disrupt existing RNA secondary structure (CHIKV-D2S). We show that CHIKV-D2S presents altered DVG generation compared to wild-type virus, correlating with its change in RNA secondary structure obtained by SHAPE-MaP. Our work thus demonstrates that RNA secondary structure impacts CHIKV DVG production during replication.

Immunosuppressed individuals, such as people living with HIV (PLWH), remain vulnerable to severe COVID-19. We analyzed the persistence of specific SARS-CoV-2 humoral and cellular immune responses in a retrospective, cross-sectional study in PLWH on antiretroviral therapy. Among 104 participants, 70.2% had anti-S IgG antibodies and 55.8% had significant neutralizing activity against the Omicron variant in a surrogate virus neutralization test. Only 38.5% were vaccinated (8.76 ± 4.1 months prior), all displaying anti-S IgG, 75% with neutralizing antibodies and anti-S IgA. 29.8% had no SARS-CoV-2 serologic markers and displayed significantly lower CD4 counts and HIV viral load. Severe immunosuppression (present in 12.5% of participants) was linked to lower levels of detectable anti-S IgG (0.0003), anti-S IgA (p &lt; 0.0001) and lack of neutralizing activity against Omicron variant (p &lt; 0.0001). T-cell responses were present in 86.7% of tested participants, even in those lacking serological markers. In PLWH without severe immunosuppression, neutralizing antibodies and T-cell responses persisted for up to 9 months post-infection or vaccination. Advanced immunosuppression led to diminished humoral immunity, but retained cellular immune.

(1) Background: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a lifesaving treatment but carries a high infection risk. Diagnosing infections remains challenging due to the limited accuracy of standard biomarkers. (2) Methods: This single-center study aimed to evaluate presepsin (PSP) and YKL-40 as infection biomarkers in febrile patients during the allo-HSCT pre-engraftment phase. Biomarker levels were prospectively measured in 61 febrile episodes from 54 allo-HSCT patients at admission, representing baseline levels and then at Day 1, 3, 5, and 7 following fever onset. The diagnostic value was compared to that of procalcitonin (PCT). (3) Results: PSP showed fair diagnostic value on Day 1 (AUC 0.656; 95% CI: 0.510 – 0.802) and Day 3 (AUC 0.698; 95% CI: 0.559 – 0.837). YKL-40 did not provide any significant diagnostic value across measured time points. PCT outperformed PSP and YKL-40, particularly on Day 3 (AUC 0.712; 95% CI: 0.572 – 0.852). When combining biomarkers, the best model for predicting infection used PSP > 3.144 ng/mL and PCT > 0.28 g/L on Day 3, resulting in R2 of about 31% (p < 0.001). (4) Conclusion: Neither test showed sufficient discriminative power for early infection to recommend their use as individual diagnostic tools in clinical practice.

In all mammals, the circulating pool of MLT is synthesized in the pineal gland, during the night darkness hours. Its main function is that of synchronizing the organism in the photoperiod. In contrast, extra-pineal MLT is synthesized in peripheral organs, does not follow any circadian rhythm nor circulates and plays a detoxifying and cytoprotective action. Circulating MLT may stimulate both innate and acquired immune responses by its circadian action and by activating high affinity receptors on immunocompetent cells. Extra-pineal MLT may have anti-oxidant and anti-inflammatory effects dampening the innate immune response. These two seemingly divergent roles may be considered as two faces of the same coin. In fact, the integration of both circulating and extra-pineal MLT functions might generate a balanced and effective immune response against microbial pathogens. The studies described in this review investigated the effect of exogenous MLT in various models of infectious diseases using extremely different doses and treatment schedules. None of them evaluated the possibility to integrate the non-circadian anti-inflammatory effect with the circadian immunoenhancing action of MLT. As a consequence, in spite that most studies agree that MLT has a beneficial effect against infections, it seems difficult to draw any definite conclusion about its possible therapeutic use.

The spread of viral pathogens both between and within hosts is inherently a spatial process. While the spatial aspects of viral spread at the epidemiological level have been increasingly well characterized, the spatial aspects of viral spread within infected hosts are still understudied. Recent experimental studies, however, have started to shed more light on the mechanisms and spatial dynamics of viral spread within hosts. Here, we review these experimental studies as well as the limited number of computational modeling efforts that have begun to integrate spatial considerations for understanding within-host viral spread. We limit our review to influenza virus to highlight key mechanisms affecting spatial aspects of viral spread for pathogens of the respiratory tract. There is considerable empirical evidence for highly spatial within-host spread of influenza virus, yet few computational modeling studies that shed light on possible factors that structure the dynamics of this spatial spread. In existing modeling studies, there is also a striking absence of theoretical expectations of how spatial dynamics may impact the dynamics of viral populations. To mitigate this, we turn to the extensive ecological and evolutionary literature to provide informed theoretical expectations for what viral and host factors may impact the spatial patterns of within-host viral dynamics and for how spatial spread will affect the genetic composition of within-host viral populations. We end by discussing current knowledge gaps related to the spatial component of within-host influenza virus spread and the potential for within-host spatial considerations to inform the development of disease control strategies.

As revealed by the recent resurgence of yellow fever virus (YFV) activity in the tropical regions of Africa and South America, YFV control measures need urgent rethinking. Over the last decade, most reported outbreaks occurred in, or eventually reached, areas of low vaccination coverage but suitable for virus transmission, with an unprecedented risk of expansion to densely populated territories in Africa, South America and Asia. As reflected in the World Health Organization’s initiative launched in 2017, it is high time to strengthen epidemiological surveillance to monitor accurately, viral dissemination and redefine vaccination recommendation areas. Vector-control and immunisation measures need to be adapted and vaccine manufacturing must be reconciled with an increasing demand. We will have to face more YF cases in the upcoming years hence, improving disease management through the development of efficient treatments will prove most beneficial. Undoubtedly, these developments will require in-depth descriptions of YFV biology at molecular, physiological and ecological levels. This second section of the two-part review describes the current state of knowledge and gaps regarding the molecular biology of YFV, along with an overview of the tools that can be used to manage the disease at the individual, local and global levels.

The recent resurgence of yellow fever virus (YFV) activity in the tropical regions of Africa and South America has sparked renewed interest in this infamous arboviral disease. YFV had been a human plague for centuries prior to the identification of its urban transmission vector, the Aedes aegypti mosquito species, and the development of an efficient live-attenuated vaccine, the YF-17D strain. The combination of vector-control measures and vaccination campaigns drastically reduced YFV incidence in humans on many occasions, but the virus never ceased to circulate in the forest, through its sylvatic invertebrate vector(s) and vertebrate host(s). Outbreaks recently reported in Central Africa (2015-2016) and Brazil (since late 2016), reached considerable proportions in terms of spatial distribution and total numbers of cases, with multiple exports, including to China. In turn, questions regarding the likeliness of occurrence of large urban YFV outbreaks in the Americas or of a successful import of YFV to Asia are currently resurfacing. This two-part review describes the current state of knowledge and gaps regarding the molecular biology and transmission dynamics of YFV, along with an overview of the tools that can be used to manage the disease at the individual, local and global levels.

Fermented foods and ingredients, including fermentates derived from lactic acid bacteria (LAB) in dairy products, can modulate the immune system. Here we describe the use of reconstituted skimmed milk powder to generate novel fermentates from Lactobacillus helveticus strains SC232, SC234, SC212, and SC210, and from Lacticaseibacillus casei strains SC209 and SC229, and demonstrate using in vitro assays that these fermentates can differentially modulate cytokine secretion by bone marrow derived dendritic cells (BMDCs) when activated with either the viral ligand, loxoribine, or an inflammatory stimulus, lipopolysaccharide. Specifically, we demonstrate that SC232 and SC234 increase cytokines IL-6, TNF-α, IL-12p40, IL-23, IL-27 and IL-10, and decreased IL-1β in primary bone marrow derived dendritic cell (BMDCs) stimulated with a viral ligand. In contrast exposure of these cells to SC212 and SC210 resulted in increased IL-10, IL-1β, IL-23, and decreased IL-12p40 following activation of the cells with the inflammatory stimulus LPS. Interestingly SC209 and SC229 had little or no effect on cytokine secretion by BMDCs. Overall, our data demonstrates that these novel fermentates have specific effects and can differentially enhance key immune mechanisms that are critical to viral immune responses, or can suppress responses involved in chronic inflammatory conditions, such as Ulcerative Colitis (UC), and Crohn’s disease (CD).

Vaccines are one of the most effective medical interventions, playing a pivotal role in treating infectious diseases. Although traditional vaccines comprising of killed, inactivated, or live attenuated pathogens have resulted in protective immune responses, negative consequences of their administration have been well-appreciated. Modern vaccines have evolved to contain purified antigenic proteins, epitopes, or antigen-encoding mRNAs, rendering them relatively safe. However, reduced humoral and cellular responses pose major challenges to modern vaccine platforms. Protein nanoparticle (PNP)-based vaccines have garnered substantial interest in recent years for their ability to present repetitive array of antigens for improving immunogenicity and enhancing protective responses. Discovery and characterization of naturally occurring PNPs from various living organisms such as bacteria, archaea, viruses, insects, and eukaryotes, as well as computationally designed structures and approaches to link antigens to the PNPs have paved the way for unprecedented advances in the field of vaccine technology. In this review, we focus on some of the widely used naturally occurring and optimally designed PNPs for their suitability as promising vaccine platforms for displaying native-like antigens from viral pathogens for protective immune responses. Such platforms hold great promise in combating emerging and re-emerging infectious diseases and enhancing vaccine efficacy and safety.

Gene therapy has seen major progress in recent years. Viral vectors have made a significant contribution through efficient engineering for improved delivery and safety. A large variety of indications such as cancer, cardiovascular, metabolic, hematological, neurological, muscular, ophthalmological, infectious diseases, and immunodeficiency have been targeted. Viral vectors based on adenoviruses, adeno-associated viruses, herpes simplex viruses, retroviruses including lentiviruses, alphaviruses, flaviviruses, measles viruses, rhabdoviruses, Newcastle disease virus, poxviruses, picornaviruses, reoviruses, and polyomaviruses have been used. Proof-of-concept has been demonstrated for different indications in animal models. Therapeutic efficacy has also been achieved in clinical trials. Several viral vector-based drugs have been approved for the treatment of cancer, and hematological, metabolic, and neurological diseases. Moreover, viral vector-based vaccines have been approved against COVID-19 and Ebola virus disease.

A recent report in PNAS that Candidatus Nanohaloarchaeum antarcticus requires haloarchaeon Halorubrum lacusprofundi for growth expands the list of known symbiotic or parasitic associations between the members of DPANN archaea, which are relatively small cells with reduced genomes and limited metabolic capacity, and free-living archaea. In line with previous studies addressing the enigmatic mechanism(s) for the transfer of metabolites from Ignicoccus hospitalis to Nanoarchaeum equitans, this new study presents additional evidence supporting a direct cytoplasmic connection facilitated by the fusion of parasite’s membrane with that of its host. Here I show that this novel mechanism for accessing the host resources by a membrane fusing mechanism, which eliminates the need for sophisticated multivalent transport systems, is fundamentally similar to that employed by several viral lineages. These new findings support an evolutionary model on the origin of incipient viral lineages from parasitic cellular lineages that started their parasitic life cycle by fusing with their host cells.

(1) Background: Hepatitis B virus (HBV) viral load (VL) is useful in determining treatment eligibility, however, due to high costs associated with the test, hepatitis B e antigen (HBeAg) is recommended as a proxy for HBV VL in resource-limited settings. (2) Methods: We used 299 archived plasma samples with hepatitis B surface antigen (HBsAg), HBeAg, and HBV VL (cut-off of 20,000 IU/mL and 200,000 IU/mL) results from people living with human immunodeficiency virus (PLWH). HBeAg and HBV VL results were analyzed to evaluate the use of HBeAg to determine CHB treatment eligibility and qualification of HBV prevention of mother-to-child transmission (PMTCT) prophylaxis for the first time in Botswana. (3) Results: Approximately 70.8% and 87.5% of participants with HBeAg-positive serology had HBV viral loads ≥20,000 IU/mL and 200,000 IU/mL respectively. Using logistic regression, the odds of having a qualifying HBV VL for CHB treatment and PMTCT prophylaxis were respectively 55.5 and 110.4 times higher in participants with positive HBeAg serology indicating a statistically significant association between HBeAg status and HBV VL. (4) Conclusions: HBeAg detection may not always correlate with high HBV VL, warranting further research focusing on this association, and other biomarkers that correlate better with HBV VL.

Artemia (brine shrimp), holds significant value as a live feed for larval fish and crustaceans, owing to their distinctive dietary requirements. However, it is vital to acknowledge that Artemia also carries potential risk as a vector of infection. We conducted a metagenomic analysis to explore the virome present in Artemia cysts collected from inland salt lakes across four distinct regions in Kazakhstan. The study identified the presence of dsDNA phages and RNA virus sequences, with a predominant representation from the Reoviridae, Nodaviridae, Dicistroviridae, Picornaviridae, Astroviridae, Tombusviridae, and Solemoviridae families. In general, this study has significantly enhanced our understanding of the virome of Artemia cysts in the saline lakes of Kazakhstan. It has also furnished crucial insights for the identification, surveillance, and management of viral infections that impact brine shrimp and fish species populations.

Worldwide, one of the main causes of death among young adults is multiple trauma. In these pa-tients hemorrhagic shock represents the leading cause for worsening of the clinical status and for increased morbidity and mortality. This is due to a multifactorial complex involving cellular, bi-ological, and biophysical mechanisms. The most important mechanisms affecting clinical out-come are oxidative stress, the augmentation of pro-inflammatory status, immune deficiency, dis-ruptions in the coagulation cascade, imbalances in electrolyte and acid-base homeostasis. Poly-trauma patients in hemorrhagic shock need adequate fluid management to ensure hemodynamic stability that must consider not only the maintenance of adequate blood pressure, but also the ad-equate oxygenation of tissues for optimal cellular function. In the current clinical practice, fluid resuscitation in polytrauma patients uses a variety of widely studied pharmacological products, such as crystalloids, colloids, blood transfusions, and the infusion of other blood products. Alt-hough these products exist, an agreement was not reached on a standard administration protocol that could be generally applied for all patients. Moreover, numerous studies have reported a se-ries of adverse events related to fluid resuscitation and to the inadequate use of these products. This review aims at describing the impact the administration of all the solutions used in fluid re-suscitation might have on the cellular and pathophysiological mechanisms in the case of poly-trauma patients suffering from hemorrhagic shock.

Abstract: The SARS-CoV-2 pandemic has reemphasized the urgent need for broad-spectrum antiviral therapies. We developed a computational workflow using scRNA-Seq data to assess cellular metabolism during viral infection. With this workflow we predicted the capacity of cells to sustain SARS-CoV-2 virion production in patients and found a tissue-wide induction of metabolic pathways that support viral replication. Expanding our analysis to influenza A and dengue viruses, we identified metabolic targets and inhibitors for potential broad-45 spectrum antiviral treatment. These targets were highly enriched for known interaction partners of all analyzed viruses. Indeed, phenformin, an NADH:ubiquinone oxidoreductase inhibitor, suppressed SARS-CoV-2 and dengue virus replication. Atpenin A5, blocking succinate dehydrogenase, inhibited SARS-CoV-2, dengue virus, respiratory syncytial virus, and influenza A with high selectivity indices. In vivo, phenformin showed antiviral activity against SARS-CoV-2 in a Syrian hamster model. Our work establishes host metabolism as druggable for broad-spectrum antiviral strategies, providing invaluable tools for pandemic preparedness.

Rabbit hemorrhagic disease virus disease 2 (RHDV2) emerged in the United States in 2018 and has spread in both domestic and wild rabbits nationwide. The virus has a high mortality rate and can spread rapidly between infected individuals. Vaccination against RHDV2 provides the best protection against disease and should be considered by all rabbit owners. Here, we investigate the duration of immunity provided by vaccination with the Medgene Platform conditionally licensed commercial vaccine 6 months following the initial series. Rabbits received either the vaccination or a placebo and were challenged with RHDV2 6 months later. All vaccinated rabbits survived challenge whereas 18/19 non-vaccinated controls succumbed to infection within 10 or fewer days post-challenge. These results demonstrate lasting immunity following vaccination with the Medgene RHDV2 vaccine.

CX3CL1, also named fractalkine or neurotactin, the only known member of the CX3C chemokine family that can chemoattract several immune cells. CX3CL1 exists in both membrane-anchored and soluble forms, each mediating distinct biological activities. CX3CL1 signals are transmitted through its unique receptor, CX3CR1, primarily expressed in microglia of central nervous system (CNS). In the CNS, CX3CL1 acts as a regulator of microglia activation in response to brain disorders or inflammation. Recently, there has been a growing interest in the roles of CX3CL1 in regulating cell adhesion, chemotaxis, and host immune response in viral infection. Here, we provide a comprehensive review of the changes and function of CX3CL1 in various viral infections such as human immunodeficiency virus (HIV), SARS-CoV-2, influenza virus and cytomegalovirus (CMV) infection, to highlight the emerging roles of CX3CL1 in viral infection and the associated diseases.

Viruses are the most common congenital infections and an important cause of fetal malformations, morbidity, and mortality. The effects of these infections, which are transmitted in-utero (transplacentally), during childbirth or in the puerperium depend on the timing of the infections. These vary from miscarriages (usually with infections in very early pregnancy), congenital malformations (where the infections occur during organogenesis) and morbidity (with infections occurring late in pregnancy, during childbirth or after delivery). The most common of these viruses are cytomegalovirus, hepatitis, parvovirus B-19, rubella, varicella and zika. There are currently very few efficacious antiviral agents licensed for use in pregnancy and therefore for most of these infections, prevention by means of immunisation (where there is a vaccine), administration of immunoglobulins to those exposed to the virus to offer passive immunity or appropriate measures to avoid being infected would be options to minimise the infections and their consequences. In this review, we discuss the current understanding of some of the congenital infections and their consequences on both the mother and fetus and their management focusing mainly on prevention.

Background: The clinical impact of vasopressin in hemorrhagic shock remains largely unknown. Objective: This systematic review and meta-analysis was designed to investigate the effects of vasopressin receptor agonists during the resuscitation of hemorrhagic shock. Methods: A systematic search of PubMed (MEDLINE), Scopus, and PubMed Central was conducted for relevant articles. Preclinical (animal) and clinical studies were included. The primary objective was to investigate the correlation of vasopressin receptor agonist use with mortality and various hemodynamic parameters. Results: Data extraction was possible in 13 animal studies and two clinical studies. Differences in risk of mortality between patients who received a vasopressin receptor agonist were not statistically significant when compared to those who were not treated with such agents [RR (95%CI): 1.17 (0.67, 2.08); p=0.562; I2 = 50%]. The available data were insufficient to conduct a meta-analysis assessing the effect of vasopressin receptor agonists on hemodynamics. Drawing safe conclusions from animal studies was challenging, due to significant heterogeneity in terms of species and dosage of vasopressin receptor agonists across studies. Conclusions: Differences in risk of mortality between patients who received a vasopressin receptor agonist were not statistically significant when compared to those who were not treated with such agents after hemorrhagic shock.

Despite effective vaccines, yellow fever outbreaks persist, increasing the urgency to find antivirals for patient treatment. This study aimed to discover compounds with potential antiviral properties against the wild-type yellow fever virus (wt-YFV) in Hippeastrum puniceum, of the Amaryllidaceae family, through bioassay-guided fractionation of the crude bulb extract using ultra-high-performance liquid chromatography (UHPLC) coupled with high-resolution ESI-QTOF mass spectrometry and subsequent analysis of the pharmacokinetic and toxicological properties (ADMET) of the annotated compounds. In the active fractions against wt-YFV, six alkaloids were proposed such as bulbisine, cathinone, trigonelline, tetrahydroharman-3-carboxylic acid, and 2,7-dimethoxyhomolycorine (or 3-O-acetylnarcissidine). Co-occurring in these fractions were the amino acids arginine, asparagine, tryptophan, and glutamic acid. In silico ADMET analysis of the alkaloids predicted good absorption, distribution, excretion, favorable metabolization profiles, and non-mutagenic toxicity, indicating their potential for drug development. These findings justify further in vitro assessment of the compounds against YFV and in vivo testing in animal models. This strategy seems to be an efficient approach for discovering antiviral compounds against YFV. Such discoveries hold promise not only in combating YFV but also in addressing a spectrum of other flaviviruses.

Alzheimer’s Disease (AD), a progressive and debilitating condition, is reported to be the most common type of dementia, with at least 55 million people believed to be currently affected. Many causation hypotheses of AD exist, yet the intriguing link between viral infection and its possible contribution to the known etiology of AD has become an attractive focal point of research for the field and a challenging study task. In this review, we will explore the historical perspective and milestones that led the field to investigate the viral connection to AD. Specifically, several viruses such as Herpes Simplex Virus 1 (HSV-1), Zika virus (ZIKV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), along with several others mentioned, include the various viruses presently considered within the field. We delve into the strong evidence implicating these viruses in the development of AD. We will also extend beyond these mere associations by carefully analyzing the potential mechanisms by which viruses may contribute to AD pathology. This includes but is not limited to direct neuronal infections, dysregulation of immune responses, and the impact on protein processing. Controversies and challenges of the viral-AD relationship emerge as we tease out these potential mechanisms considered. Looking forward, we emphasize the future directions the field should take to tackle the remaining unanswered questions and the glaring research gaps that persist. Overall, this review aims to provide a comprehensive survey of the past, present, and future of the potential link between viral infections and their association with AD development.

Viral Encephalitis is a significant public health concern globally, especially west Africa. There are more than 500 known arboviruses with over 100 of them identified to cause encephalitic diseases in humans and animals, giving rise to a tremendous burden of the diseases, and socioeconomic strains in tropical and subtropical regions worldwide. Despite their importance, few effective preventive and control measures in form of vaccines and therapeutics are available and where they are, usage is limited. These limitations are largely hinged on the paucity of information about the molecular epidemiology and transmission patterns of VE in west Africa. Here, we reviewed the transmission dynamics, ecological drivers, and molecular epidemiology of VE in the region. Collectively, timely and accurate interventions are essential for encephalitic viral disease control. Moreover, the integrated health system approach, combining surveillance, vaccination, vector control, and community engagement could be effective in preventing viral encephalitis globally.

Infection with Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) causes Coronavirus Disease 2019 (COVID-19), which has reached pandemic proportions. A number of effective vaccines have been produced, including mRNA vaccines and viral vector vaccines, which are now being implemented on a large scale in order to control the pandemic. The mRNA vaccines are composed of the Spike S1 protein encoding mRNA, incorporated in a lipid nanoparticle, stabilized by polyethylene glycol (PEG). mRNA vaccines are novel in many respects, including cellular uptake, the intracellular routing, processing, and secretion of the viral protein. Viral vector vaccines have incorporated DNA sequences encoding the SARS-CoV-2 Spike S1 protein into (attenuated) adenoviruses. The antigen presentation routes in MHC class I and class II, in relation to induction of virus neutralizing antibodies and cytotoxic T-lymphocytes will be reviewed. In rare cases, mRNA vaccines induce unwanted immune mediated side effects. mRNA based vaccines may lead to an anaphylactic reaction. This reaction may be triggered by PEG. The intracellular routing of PEG, and potential presentation in the context of CD1 will be discussed. Adenovirus vector based vaccines have been associated with thrombocytopenic thrombosis events. The anti-platelet factor 4 antibodies found in these patients could be generated due to conformational changes of relevant epitopes presented to the immune system.

Human influenza A viruses (IAVs) cause global pandemics and epidemics, which remain serious threats to public health because of the shortage of effective means of control. To combat the surge of viral outbreaks, new treatments are urgently needed. Developing new virus control modalities requires better understanding of virus-host interactions. Here we describe how IAV infection triggers cellular apoptosis, and how this process can be exploited towards development of new therapeutics, which might be more effective than the currently available anti-influenza drugs.

The presence of anti SARS-CoV2-RBD antibody (Anti-RBD) prevents severe COVID-19. We aimed to determine the accuracy of a point-of-care Anti-RBD test implemented in person living with HIV (PLWH), systemic lupus erythematosus (SLE), and chronic kidney disease (CKD). We enrolled 182 non-comorbid subjects and 335 persons with comorbid (PLWH, SLE, CKD) to test anti-RBD assay compared to surrogate viral neutralization (SVNT) as the reference test. We performed linear correlation analysis between anti-RBD vs SVNT and a ROC analyses to ascertain anti-RBD cut-off at 30%, 60%, and 90% inhibition of SVNT to calculate accuracy. Correlations of anti-RBD to SVNT among all groups were excellent with R= 0.7903, R=0.7843, R=0.8153 among non-comorbid, SLE and CKD groups, respectively, with significantly higher correlation among the PLWH group (R=0.8877; p-value=0.0072) compared to non-comorbid group. The accuracy of the anti-RBD test among PLWH and CKD group was similar with the non-comorbid but showed lower sensitivity in the SLE group (p=0.000014). The specificity of the test remained high in all groups. In conclusion, the Anti-RBD test had excellent correlation to SVNT. The persistently high specificity in all groups suggests that this test can be reliably utilized to detect presence of low neutralization capacity, prompting additional vaccination.

Disease outbreaks can severely affect populations in the wild. However, their ecological consequences are poorly understood. Here, we used a multi-site capture-recapture model to investigate the impacts of a yellow fever outbreak on the endangered golden lion tamarin Leontopithecus rosalia, in the Atlantic forest, Brazil. We show that the annual adult survival rate severely declined in 2017-2018, coinciding with the outbreak period. Simultaneously, dispersal patterns changed temporarily, with a slight reduction of dispersal between groups of the same forest fragment from 3.6 to 2.8%, and a strong increase of dispersal between forest fragments, from 0.4 to 4.3%. Those results suggest that disease transmission potential was low, especially between forest fragments and advocate for a better integration of host movements and landscape configuration when evaluating species response to vector-borne diseases

Rapid spread of African swine fever virus (ASFV), causing severe disease with often high fatality rates in Eurasian suids, prevails as a threat for pig populations and dependent industries world-wide. Although advancing scientific progress continually enhances our understanding of ASFV pathogenesis, alternative transmission routes for ASFV have yet to be assessed. Here, we demonstrate that ASFV can efficiently be transferred from infected boars to naïve recipient gilts through artificial insemination (AI). In modern pig production, semen from boar studs often supplies many sow herds. Thus, the infection of a boar stud presents the risk of rapidly and widely distributing ASFV within or between countries. Daily blood and semen collection from four boars after intramuscular inoculation with ASFV strain ‘Estonia 2014’ resulted in detection of ASFV genomes in the semen as early as 2 dpi, in blood at 1 dpi while semen quality remained largely unaffected. Ultimately, after insemination with extended semen, 7 of 14 gilts were ASFV positive by 7 days post insemination, and all gilts were ASFV positive by 35 days post insemi-nation. Twelve out of 13 gilts aborted at the onset of fever. A proportion of fetuses originating from the remaining gilt showed both abnormalities and replication of ASFV in fetal tissues. Thus, we present evidence for the efficient transmission of ASFV to gilts via AI and also to im-planted embryos. These results underline the critical role that boar semen could play in ASFV transmission.

African swine fever (ASF) has evolved from an exotic animal disease to a threat to global pig production. An important avenue for wide-spread transmission of animal diseases is the dissemination of viruses through boar semen used for artificial insemination (AI). In this context, we investigated the role of male reproductive organs in ASF. Mature domestic boars and adolescent wild boar inoculated with different ASF virus strains were investigated by means of virological and pathological methods. Additionally, electron microscopy was employed to investigate in vitro inoculated sperm. Viral genome, antigen and infectious virus could be found in all gonadal tissues and accessory sex glands. The viral antigen and viral mRNAs were mainly found in mononuclear cells of the respective tissues. However, some other cell types, including Leydig, endothelial and stromal cells were also found positive. Using RNAScope, p72 mRNA could be found in scattered halo cells of the epididymal duct epithelium which could point to disruption of the barrier. No direct infection of spermatozoa was observed by immunohistochemistry or electron microscopy. Taken together, our results strengthen the assumption that ASFV can be transmitted via boar semen. Future studies are needed to explore excretion dynamics and transmission efficiency.

In recent years, Lassa fever has been announced as an infectious disease in the world, a few imported cases have been accounted for in various pieces of the world and there are developing worries of the possibilities of Lassa fever Virus as an organic weapon. Regardless of its assaulting impact, no substantial arrangement has been created to reduce the hazard of the ailment, about a large portion of 10 years after identifying it. A Review based on the documents from the literature search on PubMed, Scopus, Goggle Scholar and Science direct. Out of these, the final 16 articles that met the criteria were selected. Relevant information on epidemiology, the burden of management and control were obtained. Timely and effective containment of the Lassa fever disease in Lassa village four decades ago could have minimized the devastating effect and threats posed by this illness in the West African sub-region and indeed the entire globe. That was a hard lesson calling for much more proactive measures towards the eradication of the illness at primary, secondary, and tertiary levels of health care. Hence, the paper is aimed at appraising the threats associated with Lassa fever disease; its demands on curtailing the menace of the epidemic, and recommendations on important focal points.

The rapid spread of African swine fever virus (ASFV), causing severe and often lethal disease in domestic pigs and Eurasian wild boar, continues to be a threat for pig populations and dependent industries. Despite scientific achievements that deepen our understanding of ASFV pathogenesis, alternative transmission routes for ASFV remain to be elucidated. We previously demonstrated the efficient transmission of ASFV from infected boars to naïve recipient gilts via artificial insemination, thereby highlighting the importance of surveillance in boar semen prior to shipment. Since accurate and reliable detection of even low amounts of ASFV in boar semen is key for disease prevention and control, we established a suitable diagnostic pipeline to efficiently detect ASFV genome in boar semen. Here, we assessed sensitivity, specificity and overall performance of various routine nucleic acid extraction kits as well as qPCR protocols in detecting ASFV genome in blood and semen of boars. Feasibility of respective kits and methods for future use in boar studs was also considered. Variability in sensitivity mostly concerned samples with low to very low amounts of ASFV genome. Ultimately, we defined a well-suited pipeline to precisely detect ASFV genome in boar semen, as early as 2 days post ASFV infection.

Apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like (APOBEC) proteins are a diverse and evolutionarily conserved family of cytidine deaminases that provide a variety of functions from tissue-specific gene expression and immunoglobulin diversity to control of viruses and retrotransposons. APOBEC family expansion has been documented among mammalian species, suggesting a powerful selection for their activity. Enzymes with a duplicated zinc-binding domain often have catalytically active and inactive domains, yet both have antiviral function. Although APOBEC antiviral function was discovered through hypermutation of HIV-1 genomes lacking an active Vif protein, much evidence indicates that APOBECs also inhibit virus replication through mechanisms other than mutagenesis. Multiple steps of the viral replication cycle may be affected, although nucleic acid replication is a primary target. Packaging of APOBECs into virions was first noted with HIV-1, yet is not a prerequisite for viral inhibition. APOBEC antagonism may occur in viral producer and recipient cells. Signatures of APOBEC activity include G-to-A and C-to-T mutations in a particular sequence context. The importance of APOBEC activity for viral inhibition is reflected in the identification of numerous viral factors, including Vif, which are dedicated to antagonism of these deaminases. Such viral antagonists often are only partially successful, leading to selection for viral variants.

Given the recent emergence of Rift Valley Fever (RVF) in Rwanda and its profound impact on livelihoods and health, improving RVF prevention and control strategies is crucial. Vaccinating livestock is one of the most sustainable strategies to mitigate the impact of RVF on health and livelihoods, yet vaccine supply chain constraints severely limit the effectiveness of vaccination programs. In the human health sector, unmanned aerial vehicles, i.e., drones, are increasingly being used to improve supply chains and last-mile vaccine delivery. We investigated perceptions on whether delivering RVF vaccines by drone in Rwanda might help to overcome logistical constraints in the vaccine supply chain. We conducted semi-structured interviews with stakeholders in the animal health sector and Zipline employees in Nyagatare District in the Eastern Province of Rwanda and used content analysis to identify key themes. We found that stakeholders in the animal health sector and Zipline employees believe that drones could improve RVF vaccination in Nyagatare. The main benefits study participants identified included decreased transportation time, improved cold chain maintenance, and cost savings.

Microbial immune escape represents the primary cause of induced pathogenesis in humans, and it represents a pivotal method used by viral agents to increase their load and suppress key mechanisms of the innate and adaptive immune system. This phenomenon represents the primary factor that led to the onset of the 1918-1920 A(H1N1) Influenza and 2020-2022 COVID-19 pandemics, and it possibly played a major role in the onset of the AIDS pandemic as well. Moreover, repeated incidents of immune evasion could be associated with higher rates of cellular aging (Jackson et al., 2017), most likely due to the consequent increased demands of energy consumption. Highly developed viral immune evasion ultimately indicates the high inner intelligence of human immunity due to reflective and imitative characteristics of reactions that are produced against initial actions. Ribonucleic acid-based viral genomes contain open reading frames, which consist of genes producing sixteen non-structural proteins. Such proteins play a considerable role in desensitizing first-line immunity during cellular infection, and non-structural proteins 1, 10 and 16 have the strongest effects against a healthy expression rate of Type I and Type III Interferon-encoding genes. Type I Interferons consist of IFN-alpha, -beta, -delta, -epsilon, -omega, -tau and -zeta, whilst Type III Interferons consist of IFN-lambda1, -lambda2 and -lambda3, and they act as stimulators of intracellular signalling cascades that in turn lead to the activation and expression of interferon-stimulated genes (Brown et al., 2022). The earlier the interferon-stimulated genes are activated, the lower the extent of pro-inflammatory mediation and overall, the more effective the antiviral immune response will be, given the exponential nature of the viral load increase. Non-structural protein 16 methylates the 5’ cap of the virus, making the pathogen-associated molecular patterns less recognisable by pattern-recognition receptors, and it requires activation by bonding with non-structural protein 10. It is preserved in the S-Adenosyl-L-Methionine pocket of the SARS-CoV-2 genome. Non-structural protein 1 (NS1) directly cleaves the host cell mRNA producing Type I and possibly Type III Interferons, thereby preventing a translation process of the immune proteins. NS1 has recently been found to often be packaged into exosomes once secreted by the viral genome in the cytosol, meaning that exocytosis and paracrine signalling to neighbouring cells before their actual infection is possible. As a result, NS1 is highly capable of silencing the first-line immune responses of uninfected neighbouring cells as well, thereby highlighting the need to adjust the focus of therapeutics and vaccinology toward first-line immunity and further indicating its foundational importance in the support for the development of precise and balanced defenses against microbial agents of concern (EL SAFADI et al., 2022).

Antiviral drugs cannot treat dengue fever, a serious medical disease spread by the Aedes aegypti and Aedes albopictus mosquitoes. One important arbovirus disease is dengue fever. Safe, affordable and effective drugs that inhibit dengue virus (DENV) are needed to control dengue worldwide. Medicinal plants have long been considered an important alternative in the treatment of various diseases, including dengue fever. The aim of this study was to use databases PubMed, Google Scholar and Research Gate to identify plants of different tribes from different places that can be used for the treatment of DENV infection and open supportive care for dengue. Previous studies have shown antiviral activity of medicinal plants against DENV. The aim of the present study is to discover plants from different tribes from different places that can be used to treat DENV infection and provide open supportive care against dengue. The recommended reporting guidelines for systematic reviews and meta-analyses (PRISMA statement) were followed in the search and selection of articles using the PubMed database, Google Scholar and Research Gate. The final selection was made after careful consideration and up to 85 publications that met the inclusion criteria. It is said that different plants from different tribes and geographical locations can be used to treat DENV infection.

Zika virus (ZIKV) is a flavivirus that originated in Africa but emerged in Latin America in 2015. In this region, other flaviviruses such as Dengue (DENV), West Nile, and Yellow Fever Virus (YFV) also circulate, allowing for possible antigenic cross-reactivity to impact viral infections and immune responses. Studies have found antibody mediated enhancement between DENV and ZIKV, but the impact of YFV antibodies on ZIKV infection has not been fully explored. ZIKV infections cause congenital syndromes, such as microcephaly, necessitating further research into ZIKV vertical transmission through the placental barrier. Recent advancements in biomedical engineering have generated co-culture methods that allow for in vitro recapitulation of the maternal: fetal interface. This study utilized a transwell assay, which is a co-culture model utilizing human placental syncytiotrophoblasts, fetal umbilical cells, and a differentiating embryoid body to replicate the maternal: fetal axis. To determine if cross reactive YFV vaccine antibodies impact the pathogenesis of ZIKV across the maternal fetal axis, maternal syncytiotrophoblasts were inoculated with ZIKV or ZIKV incubated with YFV vaccine anti-sera, and viral load was measured 72 hours post inoculation. Here we report that BeWo and HUVEC cells are permissive to ZIKV and that the impact of YFV post-vaccination antibodies on ZIKV replication is cell line dependent. Embryoid bodies are also permissive to ZIKV and the presence of YFV antibodies collected 1 to 6 months post vaccination enhances ZIKV infection. Our data show that each of the cell lines and EBs have a unique response to ZIKV complexed with post-vaccination serum suggesting there may be cell-specific mechanisms that impact congenital ZIKV infections. Since ZIKV infections can cause severe congenital syndromes, it is crucial to understand any potential enhancement or protection offered from cross-reactive, post-vaccination antibodies.

Zika virus (ZIKV) is a flavivirus that originated in Africa but emerged in Latin America in 2015. In this region, other flaviviruses such as Dengue (DENV), West Nile, and Yellow Fever Virus (YFV) also circulate, allowing for possible antigenic cross-reactivity to impact viral infections and immune responses. Studies have found antibody mediated enhancement between DENV and ZIKV, but the impact of YFV antibodies on ZIKV infection has not been fully explored. ZIKV infections cause congenital syndromes, such as microcephaly, necessitating further research into ZIKV vertical transmission through the placental barrier. Recent advancements in biomedical engineering have generated co-culture methods that allow for in vitro recapitulation of the maternal: fetal interface. This study utilized a transwell assay, which is a co-culture model utilizing human placental syncytiotrophoblasts, fetal umbilical cells, and a differentiating embryoid body to replicate the maternal: fetal axis. To determine if cross reactive YFV vaccine antibodies impact the pathogenesis of ZIKV across the maternal fetal axis, maternal syncytiotrophoblasts were inoculated with ZIKV or ZIKV incubated with YFV vaccine anti-sera, and viral load was measured 72 hours post inoculation. The data show that the impact of YFV on ZIKV replication is cell line dependent. In differentiating embryoids, the presence of YFV antibodies enhanced ZIKV infection. Since viral pathogenesis, and the impact of antigenic cross-reactive antibodies, is cell line specific at the maternal-fetal axis, this suggests there may be discreet mechanisms that impact congenital ZIKV infections.