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Updated: Jul 13, 2026

Dissecting Innate Immune Signaling in Viral Evasion of Cytokine Production
Published on: March 2, 2014
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,
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-kappaB. 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)-1beta, and expression of vPOPs causes activation of NF-kappaB.
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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