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Table of Contents

April 2018

Cover

Evidence that HIV-1 Gag is recruited into small RNA granules that contain DDX6 but are largely distinct from P bodies
Issue Image

293T cells were mock transfected or transfected with an HIV-1 provirus encoding the Gag G2A mutant, which is arrested in the cytoplasm. Columns (left to right, with nuclei in blue): DDX6 IF reveals green foci seen at low gain/magnification representing P bodies; proximity ligation assay shows sites of DDX6-Gag G2A colocalization as red spots; and merge. Insets show cells at high gain/magnification. Angled arrows allow matching of P bodies between insets and low power fields. Dotted oval contains foci that are too small to be P bodies, and could represent smaller DDX6 foci that can be co-opted by Gag proteins. Lingappa et al.

Image Credit: Brook Barajas and Jaisri Lingappa, University of Washington

Pearls

How to combat emerging artemisinin resistance: Lessons from “The Three Little Pigs”

Thanat Chookajorn

PLOS Pathogens: published April 26, 2018 | https://doi.org/10.1371/journal.ppat.1006923

Nucleated red blood cells: Immune cell mediators of the antiviral response

Ivan Nombela, Maria del Mar Ortega-Villaizan

PLOS Pathogens: published April 26, 2018 | https://doi.org/10.1371/journal.ppat.1006910

Antibiotic interceptors: Creating safe spaces for bacteria

Akshay Sabnis, Elizabeth V. K. Ledger, Vera Pader, Andrew M. Edwards

PLOS Pathogens: published April 19, 2018 | https://doi.org/10.1371/journal.ppat.1006924

Disabling of lymphocyte immune response by Ebola virus

Patrick Younan, Mathieu Iampietro, Alexander Bukreyev

PLOS Pathogens: published April 12, 2018 | https://doi.org/10.1371/journal.ppat.1006932

Metabolomics: Eavesdropping on silent conversations between hosts and their unwelcome guests

Sydney N. Newsom, Laura-Isobel McCall

PLOS Pathogens: published April 5, 2018 | https://doi.org/10.1371/journal.ppat.1006926

Polyvalent vaccines: High-maintenance heroes

Barbara Schlingmann, Katelyn R. Castiglia, Christopher C. Stobart, Martin L. Moore

PLOS Pathogens: published April 5, 2018 | https://doi.org/10.1371/journal.ppat.1006904

Review

ROS and Trypanosoma cruzi: Fuel to infection, poison to the heart

Claudia N. Paiva, Emiliano Medei, Marcelo T. Bozza

PLOS Pathogens: published April 19, 2018 | https://doi.org/10.1371/journal.ppat.1006928

Research Matters

The best laid plans of mice and women

Susan R. Ross

PLOS Pathogens: published April 12, 2018 | https://doi.org/10.1371/journal.ppat.1006873

Research Articles

Immunophenotypic characterization of CSF B cells in virus-associated neuroinflammatory diseases

Yoshimi Enose-Akahata, Shila Azodi, Bryan R. Smith, Bridgette Jeanne Billioux, Ashley Vellucci, Nyater Ngouth, Yuetsu Tanaka, Joan Ohayon, Irene Cortese, Avindra Nath, Steven Jacobson

PLOS Pathogens: published April 30, 2018 | https://doi.org/10.1371/journal.ppat.1007042

HCMV triggers frequent and persistent UL40-specific unconventional HLA-E-restricted CD8 T-cell responses with potential autologous and allogeneic peptide recognition

Nicolas Jouand, Céline Bressollette-Bodin, Nathalie Gérard, Magali Giral, Pierrick Guérif, Audrey Rodallec, Romain Oger, Tiphaine Parrot, Mathilde Allard, Anne Cesbron-Gautier, Nadine Gervois, Béatrice Charreau

PLOS Pathogens: published April 30, 2018 | https://doi.org/10.1371/journal.ppat.1007041

EBV persistence without its EBNA3A and 3C oncogenes in vivo

Anita Murer, Donal McHugh, Nicole Caduff, Jens Kalchschmidt, Mario Barros, Andrea Zbinden, Riccarda Capaul, Gerald Niedobitek, Martin Allday, Obinna Chijioke, Christian Münz

PLOS Pathogens: published April 30, 2018 | https://doi.org/10.1371/journal.ppat.1007039

Phospholipase A2 activity during the replication cycle of the flavivirus West Nile virus

Susann Liebscher, Rebecca L. Ambrose, Turgut E. Aktepe, Andrea Mikulasova, Julia E. Prier, Leah K. Gillespie, Adam J. Lopez-Denman, Thusitha W. T. Rupasinghe, Dedreia Tull, Malcolm J. McConville, Jason M. Mackenzie

PLOS Pathogens: published April 30, 2018 | https://doi.org/10.1371/journal.ppat.1007029

The SecA2 pathway of Mycobacterium tuberculosis exports effectors that work in concert to arrest phagosome and autophagosome maturation

Katelyn E. Zulauf, Jonathan Tabb Sullivan, Miriam Braunstein

PLOS Pathogens: published April 30, 2018 | https://doi.org/10.1371/journal.ppat.1007011

Varicella zoster virus productively infects human natural killer cells and manipulates phenotype

Tessa Mollie Campbell, Brian Patrick McSharry, Megan Steain, Thomas Myles Ashhurst, Barry Slobedman, Allison Abendroth

PLOS Pathogens: published April 30, 2018 | https://doi.org/10.1371/journal.ppat.1006999

Viral targeting of TFIIB impairs de novo polymerase II recruitment and affects antiviral immunity

Darya A. Haas, Arno Meiler, Katharina Geiger, Carola Vogt, Ellen Preuss, Georg Kochs, Andreas Pichlmair

PLOS Pathogens: published April 30, 2018 | https://doi.org/10.1371/journal.ppat.1006980

Multiple poliovirus-induced organelles suggested by comparison of spatiotemporal dynamics of membranous structures and phosphoinositides

Hyung S. Oh, Sravani Banerjee, David Aponte-Diaz, Suresh D. Sharma, Jason Aligo, Maria F. Lodeiro, Gang Ning, Rajni Sharma, Jamie J. Arnold, Craig E. Cameron

PLOS Pathogens: published April 27, 2018 | https://doi.org/10.1371/journal.ppat.1007036

Macrophage migration inhibitory factor is critical for dengue NS1-induced endothelial glycocalyx degradation and hyperpermeability

Hong-Ru Chen, Chiao-Hsuan Chao, Ching-Chuan Liu, Tzong-Shiann Ho, Huey-Pin Tsai, Guey-Chuen Perng, Yee-Shin Lin, Jen-Ren Wang, Trai-Ming Yeh

PLOS Pathogens: published April 27, 2018 | https://doi.org/10.1371/journal.ppat.1007033

Extracellular adenosine modulates host-pathogen interactions through regulation of systemic metabolism during immune response in Drosophila

Adam Bajgar, Tomas Dolezal

PLOS Pathogens: published April 27, 2018 | https://doi.org/10.1371/journal.ppat.1007022

Interferon induced protein 35 exacerbates H5N1 influenza disease through the expression of IL-12p40 homodimer

Anshu P. Gounder, Christine C. Yokoyama, Nicholas N. Jarjour, Traci L. Bricker, Brian T. Edelson, Adrianus C. M. Boon

PLOS Pathogens: published April 26, 2018 | https://doi.org/10.1371/journal.ppat.1007001

Cross-sectional analysis of CD8 T cell immunity to human herpesvirus 6B

Larissa K. Martin, Alexandra Hollaus, Anna Stahuber, Christoph Hübener, Alessia Fraccaroli, Johanna Tischer, Andrea Schub, Andreas Moosmann

PLOS Pathogens: published April 26, 2018 | https://doi.org/10.1371/journal.ppat.1006991

Matrix metalloproteinase inhibitors enhance the efficacy of frontline drugs against Mycobacterium tuberculosis

Yitian Xu, Lihua Wang, Matthew D. Zimmerman, Kai-Yuan Chen, Lu Huang, Dah-Jiun Fu, Firat Kaya, Nikolai Rakhilin, Evgeniya V. Nazarova, Pengcheng Bu, Veronique Dartois, David G. Russell, Xiling Shen

PLOS Pathogens: published April 26, 2018 | https://doi.org/10.1371/journal.ppat.1006974

CADM1 is essential for KSHV-encoded vGPCR-and vFLIP-mediated chronic NF-κB activation

Richard Hunte, Patricia Alonso, Remy Thomas, Cassandra Alexandria Bazile, Juan Carlos Ramos, Louise van der Weyden, Juan Dominguez-Bendala, Wasif Noor Khan, Noula Shembade

PLOS Pathogens: published April 26, 2018 | https://doi.org/10.1371/journal.ppat.1006968

MoYvh1 subverts rice defense through functions of ribosomal protein MoMrt4 in Magnaporthe oryzae

Xinyu Liu, Jie Yang, Bin Qian, Yongchao Cai, Xi Zou, Haifeng Zhang, Xiaobo Zheng, Ping Wang, Zhengguang Zhang

PLOS Pathogens: published April 23, 2018 | https://doi.org/10.1371/journal.ppat.1007016

The KAT5-Acetyl-Histone4-Brd4 axis silences HIV-1 transcription and promotes viral latency

Zichong Li, Uri Mbonye, Zeming Feng, Xiaohui Wang, Xiang Gao, Jonathan Karn, Qiang Zhou

PLOS Pathogens: published April 23, 2018 | https://doi.org/10.1371/journal.ppat.1007012

Cryo-EM structure of infectious bronchitis coronavirus spike protein reveals structural and functional evolution of coronavirus spike proteins

Jian Shang, Yuan Zheng, Yang Yang, Chang Liu, Qibin Geng, Chuming Luo, Wei Zhang, Fang Li

PLOS Pathogens: published April 23, 2018 | https://doi.org/10.1371/journal.ppat.1007009

PgaB orthologues contain a glycoside hydrolase domain that cleaves deacetylated poly-β(1,6)-N-acetylglucosamine and can disrupt bacterial biofilms

Dustin J. Little, Roland Pfoh, François Le Mauff, Natalie C. Bamford, Christina Notte, Perrin Baker, Manita Guragain, Howard Robinson, Gerald B. Pier, Mark Nitz, Rajendar Deora, Donald C. Sheppard, P. Lynne Howell

PLOS Pathogens: published April 23, 2018 | https://doi.org/10.1371/journal.ppat.1006998

HIV-1 adaptation studies reveal a novel Env-mediated homeostasis mechanism for evading lethal hypermutation by APOBEC3G

Terumasa Ikeda, Menelaos Symeonides, John S. Albin, Ming Li, Markus Thali, Reuben S. Harris

PLOS Pathogens: published April 20, 2018 | https://doi.org/10.1371/journal.ppat.1007010

Type I interferon signaling attenuates regulatory T cell function in viral infection and in the tumor microenvironment

Arunakumar Gangaplara, Craig Martens, Eric Dahlstrom, Amina Metidji, Ameya S. Gokhale, Deborah D. Glass, Maria Lopez-Ocasio, Rachel Baur, Kishore Kanakabandi, Stephen F. Porcella, Ethan M. Shevach

PLOS Pathogens: published April 19, 2018 | https://doi.org/10.1371/journal.ppat.1006985

Differential impact of transplantation on peripheral and tissue-associated viral reservoirs: Implications for HIV gene therapy

Christopher W. Peterson, Jianbin Wang, Claire Deleage, Sowmya Reddy, Jasbir Kaur, Patricia Polacino, Andreas Reik, Meei-Li Huang, Keith R. Jerome, Shiu-Lok Hu, Michael C. Holmes, Jacob D. Estes, Hans-Peter Kiem

PLOS Pathogens: published April 19, 2018 | https://doi.org/10.1371/journal.ppat.1006956

Infant transmitted/founder HIV-1 viruses from peripartum transmission are neutralization resistant to paired maternal plasma

Amit Kumar, Claire E. P. Smith, Elena E. Giorgi, Joshua Eudailey, David R. Martinez, Karina Yusim, Ayooluwa O. Douglas, Lisa Stamper, Erin McGuire, Celia C. LaBranche, David C. Montefiori, Genevieve G. Fouda, Feng Gao, Sallie R. Permar

PLOS Pathogens: published April 19, 2018 | https://doi.org/10.1371/journal.ppat.1006944

Actin polymerization in the endosomal pathway, but not on the Coxiella-containing vacuole, is essential for pathogen growth

Heather E. Miller, Charles L. Larson, Robert A. Heinzen

PLOS Pathogens: published April 18, 2018 | https://doi.org/10.1371/journal.ppat.1007005

Clostridium sordellii outer spore proteins maintain spore structural integrity and promote bacterial clearance from the gastrointestinal tract

Rebecca Rabi, Sarah Larcombe, Rommel Mathias, Sheena McGowan, Milena Awad, Dena Lyras

PLOS Pathogens: published April 18, 2018 | https://doi.org/10.1371/journal.ppat.1007004

Identifying the assembly intermediate in which Gag first associates with unspliced HIV-1 RNA suggests a novel model for HIV-1 RNA packaging

Brook C. Barajas, Motoko Tanaka, Bridget A. Robinson, Daryl J. Phuong, Kasana Chutiraka, Jonathan C. Reed, Jaisri R. Lingappa

PLOS Pathogens: published April 17, 2018 | https://doi.org/10.1371/journal.ppat.1006977

Loss of CXCR6 coreceptor usage characterizes pathogenic lentiviruses

Katherine S. Wetzel, Yanjie Yi, Anjana Yadav, Anya M. Bauer, Ezekiel A. Bello, Dino C. Romero, Frederic Bibollet-Ruche, Beatrice H. Hahn, Mirko Paiardini, Guido Silvestri, Martine Peeters, Ronald G. Collman

PLOS Pathogens: published April 16, 2018 | https://doi.org/10.1371/journal.ppat.1007003

N6-methyladenosine modification and the YTHDF2 reader protein play cell type specific roles in lytic viral gene expression during Kaposi's sarcoma-associated herpesvirus infection

Charles R. Hesser, John Karijolich, Dan Dominissini, Chuan He, Britt A. Glaunsinger

PLOS Pathogens: published April 16, 2018 | https://doi.org/10.1371/journal.ppat.1006995

KSHV induces immunoglobulin rearrangements in mature B lymphocytes

Jennifer Totonchy, Jessica M. Osborn, Amy Chadburn, Ramina Nabiee, Lissenya Argueta, Geoffrey Mikita, Ethel Cesarman

PLOS Pathogens: published April 16, 2018 | https://doi.org/10.1371/journal.ppat.1006967

Tissue maintenance of CMV-specific inflationary memory T cells by IL-15

Nicolas S. Baumann, Nicole Torti, Suzanne P. M. Welten, Isabel Barnstorf, Mariana Borsa, Katharina Pallmer, Jennifer D. Oduro, Luka Cicin-Sain, Koichi Ikuta, Burkhard Ludewig, Annette Oxenius

PLOS Pathogens: published April 13, 2018 | https://doi.org/10.1371/journal.ppat.1006993

A novel mechanism of RNase L inhibition: Theiler's virus L* protein prevents 2-5A from binding to RNase L

Melissa Drappier, Babal Kant Jha, Sasha Stone, Ruth Elliott, Rong Zhang, Didier Vertommen, Susan R. Weiss, Robert H. Silverman, Thomas Michiels

PLOS Pathogens: published April 13, 2018 | https://doi.org/10.1371/journal.ppat.1006989

Limited immune surveillance in lymphoid tissue by cytolytic CD4+ T cells during health and HIV disease

Marcus Buggert, Son Nguyen, Laura M. McLane, Maria Steblyanko, Nadia Anikeeva, Dominic Paquin-Proulx, Perla M. Del Rio Estrada, Yuria Ablanedo-Terrazas, Kajsa Noyan, Morgan A. Reuter, Korey Demers, Johan K. Sandberg, Michael A. Eller, Hendrik Streeck, Marianne Jansson, Piotr Nowak, Anders Sönnerborg, David H. Canaday, Ali Naji, E. John Wherry, Merlin L. Robb, Steven G. Deeks, Gustavo Reyes-Teran, Yuri Sykulev, Annika C. Karlsson, Michael R. Betts

PLOS Pathogens: published April 13, 2018 | https://doi.org/10.1371/journal.ppat.1006973

Host Pah1p phosphatidate phosphatase limits viral replication by regulating phospholipid synthesis

Zhenlu Zhang, Guijuan He, Gil-Soo Han, Jiantao Zhang, Nicholas Catanzaro, Arturo Diaz, Zujian Wu, George M. Carman, Lianhui Xie, Xiaofeng Wang

PLOS Pathogens: published April 12, 2018 | https://doi.org/10.1371/journal.ppat.1006988

Host shifts result in parallel genetic changes when viruses evolve in closely related species

Ben Longdon, Jonathan P. Day, Joel M. Alves, Sophia C. L. Smith, Thomas M. Houslay, John E. McGonigle, Lucia Tagliaferri, Francis M. Jiggins

PLOS Pathogens: published April 12, 2018 | https://doi.org/10.1371/journal.ppat.1006951

Evolution of structural diversity of trichothecenes, a family of toxins produced by plant pathogenic and entomopathogenic fungi

Robert H. Proctor, Susan P. McCormick, Hye-Seon Kim, Rosa E. Cardoza, April M. Stanley, Laura Lindo, Amy Kelly, Daren W. Brown, Theresa Lee, Martha M. Vaughan, Nancy J. Alexander, Mark Busman, Santiago Gutiérrez

PLOS Pathogens: published April 12, 2018 | https://doi.org/10.1371/journal.ppat.1006946

Zika virus infection in immunocompetent pregnant mice causes fetal damage and placental pathology in the absence of fetal infection

Frank M. Szaba, Michael Tighe, Lawrence W. Kummer, Kathleen G. Lanzer, Jerrold M. Ward, Paula Lanthier, In-Jeong Kim, Atsuo Kuki, Marcia A. Blackman, Stephen J. Thomas, Jr-Shiuan Lin

PLOS Pathogens: published April 10, 2018 | https://doi.org/10.1371/journal.ppat.1006994

HIV-specific Fc effector function early in infection predicts the development of broadly neutralizing antibodies

Simone I. Richardson, Amy W. Chung, Harini Natarajan, Batsirai Mabvakure, Nonhlanhla N. Mkhize, Nigel Garrett, Salim Abdool Karim, Penny L. Moore, Margaret E. Ackerman, Galit Alter, Lynn Morris

PLOS Pathogens: published April 9, 2018 | https://doi.org/10.1371/journal.ppat.1006987

An ADAM-10 dependent EPCR shedding links meningococcal interaction with endothelial cells to purpura fulminans

Hervé Lécuyer, Zoé Virion, Jean-Philippe Barnier, Soraya Matczak, Sandrine Bourdoulous, Elsa Bianchini, François Saller, Delphine Borgel, Xavier Nassif, Mathieu Coureuil

PLOS Pathogens: published April 9, 2018 | https://doi.org/10.1371/journal.ppat.1006981

STAT3 activation by E6 is essential for the differentiation-dependent HPV18 life cycle

Ethan L. Morgan, Christopher W. Wasson, Lucy Hanson, David Kealy, Ieisha Pentland, Victoria McGuire, Cinzia Scarpini, Nicholas Coleman, J. Simon C. Arthur, Joanna L. Parish, Sally Roberts, Andrew Macdonald

PLOS Pathogens: published April 9, 2018 | https://doi.org/10.1371/journal.ppat.1006975

Viral chimeras decrypt the role of enterovirus capsid proteins in viral tropism, acid sensitivity and optimal growth temperature

Léna Royston, Manel Essaidi-Laziosi, Francisco J. Pérez-Rodríguez, Isabelle Piuz, Johan Geiser, Karl-Heinz Krause, Song Huang, Samuel Constant, Laurent Kaiser, Dominique Garcin, Caroline Tapparel

PLOS Pathogens: published April 9, 2018 | https://doi.org/10.1371/journal.ppat.1006962

Protection by and maintenance of CD4 effector memory and effector T cell subsets in persistent malaria infection

Michael M. Opata, Samad A. Ibitokou, Victor H. Carpio, Karis M. Marshall, Brian E. Dillon, Jordan C. Carl, Kyle D. Wilson, Christine M. Arcari, Robin Stephens

PLOS Pathogens: published April 9, 2018 | https://doi.org/10.1371/journal.ppat.1006960

Infection history of the blood-meal host dictates pathogenic potential of the Lyme disease spirochete within the feeding tick vector

Bharti Bhatia, Chad Hillman, Valentina Carracoi, Britney N. Cheff, Kit Tilly, Patricia A. Rosa

PLOS Pathogens: published April 5, 2018 | https://doi.org/10.1371/journal.ppat.1006959

Clarithromycin expands CD11b+Gr-1+ cells via the STAT3/Bv8 axis to ameliorate lethal endotoxic shock and post-influenza bacterial pneumonia

Ho Namkoong, Makoto Ishii, Hideki Fujii, Kazuma Yagi, Takahiro Asami, Takanori Asakura, Shoji Suzuki, Ahmed E. Hegab, Hirofumi Kamata, Sadatomo Tasaka, Koji Atarashi, Nobuhiro Nakamoto, Satoshi Iwata, Kenya Honda, Takanori Kanai, Naoki Hasegawa, Shigeo Koyasu, Tomoko Betsuyaku

PLOS Pathogens: published April 5, 2018 | https://doi.org/10.1371/journal.ppat.1006955

The impact of serotype-specific vaccination on phylodynamic parameters of Streptococcus pneumoniae and the pneumococcal pan-genome

Taj Azarian, Lindsay R. Grant, Brian J. Arnold, Laura L. Hammitt, Raymond Reid, Mathuram Santosham, Robert Weatherholtz, Novalene Goklish, Claudette M. Thompson, Stephen D. Bentley, Katherine L. O’Brien, William P. Hanage, Marc Lipsitch

PLOS Pathogens: published April 4, 2018 | https://doi.org/10.1371/journal.ppat.1006966

A fine-tuned vector-parasite dialogue in tsetse's cardia determines peritrophic matrix integrity and trypanosome transmission success

Aurélien Vigneron, Emre Aksoy, Brian L. Weiss, Xiaoli Bing, Xin Zhao, Erick O. Awuoche, Michelle B. O'Neill, Yineng Wu, Geoffrey M. Attardo, Serap Aksoy

PLOS Pathogens: published April 3, 2018 | https://doi.org/10.1371/journal.ppat.1006972

Mutations in the pantothenate kinase of Plasmodium falciparum confer diverse sensitivity profiles to antiplasmodial pantothenate analogues

Erick T. Tjhin, Christina Spry, Alan L. Sewell, Annabelle Hoegl, Leanne Barnard, Anna E. Sexton, Ghizal Siddiqui, Vanessa M. Howieson, Alexander G. Maier, Darren J. Creek, Erick Strauss, Rodolfo Marquez, Karine Auclair, Kevin J. Saliba

PLOS Pathogens: published April 3, 2018 | https://doi.org/10.1371/journal.ppat.1006918

STING agonists enable antiviral cross-talk between human cells and confer protection against genital herpes in mice

Morten K. Skouboe, Alice Knudsen, Line S. Reinert, Cedric Boularan, Thierry Lioux, Eric Perouzel, Martin K. Thomsen, Søren R. Paludan

PLOS Pathogens: published April 2, 2018 | https://doi.org/10.1371/journal.ppat.1006976