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

Andrea Dorfleutner, Siera J. Talbott, Nicole B. Bryan, Kristin N. Funya, Stephanie L. Rellick, John C. Reed, Xianglin Shi, Yon Rojanasakul, Daniel C. Flynn, Christian Stehlik

Research output: Contribution to journalArticlepeer-review

75 Scopus citations

Abstract

PYRIN domain (PYD) proteins have recently emerged as important signaling molecules involved in the development of innate immunity to intracellular pathogens through activation of inflammatory mediator pathways. ASC is the central adaptor protein, which links pathogen recognition by PYD-containing pathogen recognition receptors to the activation of downstream effectors, including activation of Caspase-1 and NF-κB. The cellular PYD-only protein 1 (cPOP1) can block the recruitment of ASC to activated PAN receptors and thereby functions as an endogenous inhibitor of the PYD-mediated signal transduction pathway. Here we describe the identification and characterization of a Shope Fibroma homolog to cPOP1. Like cPOP1, a Shope Fibroma virus-encoded POP (vPOP), co-localizes and directly associates with ASC and inhibits PYD-mediated signal transduction. Poxviruses are known to encode immune evasive proteins to promote host cell infection and suppression of the host immune response. Poxvirus-encoded vPOPs represent a novel class of immune evasive proteins and impair the host response by blocking Cryopyrin and ASC inflammasome-mediated activation of pro-Caspase-1 and subsequent processing of pro-interleukin (IL)-1β, and expression of vPOPs causes activation of NF-κB.

Original languageEnglish
Pages (from-to)685-694
Number of pages10
JournalVirus Genes
Volume35
Issue number3
DOIs
StatePublished - Dec 2007

Bibliographical note

Funding Information:
Acknowledgments The project described was supported by Grant Number 5P20-RR-016440 (CS, DCF) from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH) and Grant Numbers 1R21-AI-067680 (CS), 1R03-AI-067806 (CS), and R 01-AI-56324 (JCR) from NIAID/NIH. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of NCRR or NIH. We are also grateful to the support from the Alexander Bland Osborn Cancer Center Endowment (CS).

Keywords

  • Caspase-1
  • IL-1β
  • Inflammasome
  • NF-κB
  • PYRIN domain
  • Poxvirus

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Virology

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