A Shope Fibroma virus PYRIN-only protein modulates the host immune response

Andrea Dorfleutner1, Siera J Talbott, Nicole B Bryan

  • 1Mary Babb Randolph Cancer Center and Department of Microbiology, Immunology & Cell Biology, West Virginia University School of Medicine, 1826 MBRCC, 1 Medical Center Drive, Morgantown, WV 26506-9300, USA,

Virus Genes
|August 7, 2007
PubMed

Insights

Shope Fibroma virus encodes a protein that inhibits innate immunity by blocking ASC inflammasome activation. This viral protein (vPOP) impairs host defense against intracellular pathogens.

Area of Science:

  • Innate immunity
  • Molecular signaling
  • Virology

Background:

  • PYRIN domain (PYD) proteins are key in innate immunity against pathogens.
  • ASC adaptor protein links pathogen recognition to inflammatory pathways like Caspase-1 and NF-kappaB activation.
  • Cellular PYD-only protein 1 (cPOP1) inhibits PYD signaling by blocking ASC recruitment.

Purpose of the Study:

  • To identify and characterize a Shope Fibroma virus homolog of cPOP1.
  • To investigate the role of this viral protein (vPOP) in modulating host innate immunity.

Main Methods:

  • Protein identification and characterization.
  • Co-localization and direct association assays with ASC.
  • Analysis of inflammasome activation (Caspase-1, IL-1beta processing) and NF-kappaB activation.

Main Results:

  • A Shope Fibroma virus protein (vPOP) homologous to cPOP1 was identified.
  • vPOP co-localizes with and directly binds to ASC.
  • vPOP inhibits PYD-mediated signal transduction, blocking Cryopyrin and ASC inflammasome activation, pro-Caspase-1 processing, and IL-1beta release.
  • vPOP expression leads to NF-kappaB activation.

Conclusions:

  • Poxviruses encode vPOPs as a novel class of immune evasive proteins.
  • vPOPs suppress host immune responses by inhibiting inflammasome activation and promoting viral infection.
  • vPOPs represent a new mechanism for viral immune evasion targeting PYD signaling pathways.

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