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Measles virus V protein inhibits NLRP3 inflammasome-mediated interleukin-1β secretion

J Virol. 2011 Dec;85(24):13019-26. doi: 10.1128/JVI.05942-11. Epub 2011 Oct 12.

Abstract

Inflammasomes are cytosolic protein complexes that stimulate the activation of caspase-1, which in turn induces the secretion of the inflammatory cytokines Interleukin-1β (IL-1β) and IL-18. Recent studies have indicated that the inflammasome known as the NOD-like-receptor-family, pyrin domain-containing 3 (NLRP3) inflammasome recognizes several RNA viruses, including the influenza and encephalomyocarditis viruses, whereas the retinoic acid-inducible gene I (RIG-I) inflammasome may detect vesicular stomatitis virus. We demonstrate that measles virus (MV) infection induces caspase-1-dependent IL-1β secretion in the human macrophage-like cell line THP-1. Gene knockdown experiments indicated that IL-1β secretion in MV-infected THP-1 cells was mediated by the NLRP3 inflammasome but not the RIG-I inflammasome. MV produces the nonstructural V protein, which has been shown to antagonize host innate immune responses. The recombinant MV lacking the V protein induced more IL-1β than the parental virus. THP-1 cells stably expressing the V protein suppressed NLRP3 inflammasome-mediated IL-1β secretion. Furthermore, coimmunoprecipitation assays revealed that the V protein interacts with NLRP3 through its carboxyl-terminal domain. NLRP3 was located in cytoplasmic granular structures in THP-1 cells stably expressing the V protein, but upon inflammasome activation, NLRP3 was redistributed to the perinuclear region, where it colocalized with the V protein. These results indicate that the V protein of MV suppresses NLRP3 inflammasome-mediated IL-1β secretion by directly or indirectly interacting with NLRP3.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carrier Proteins / antagonists & inhibitors*
  • Cell Line
  • Humans
  • Immune Evasion*
  • Inflammasomes / immunology*
  • Interleukin-1beta / metabolism*
  • Macrophages / immunology
  • Macrophages / virology
  • Measles virus / immunology*
  • Measles virus / pathogenicity*
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Phosphoproteins / metabolism*
  • Protein Binding
  • Protein Interaction Mapping
  • Viral Proteins / metabolism*

Substances

  • Carrier Proteins
  • Inflammasomes
  • Interleukin-1beta
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • NLRP3 protein, human
  • Phosphoproteins
  • V protein, measles virus
  • Viral Proteins