A Shope Fibroma virus PYRIN-only protein modulates the host immune response.
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.
Mary 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,
Andrea
A
Dorfleutner
Siera J
SJ
Talbott
Nicole B
NB
Bryan
Kristin N
KN
Funya
Stephanie L
SL
Rellick
John C
JC
Reed
Xianglin
X
Shi
Yon
Y
Rojanasakul
Daniel C
DC
Flynn
Christian
C
Stehlik
D000818:Animals; D019677:Artificial Gene Fusion; D053468:CARD Signaling Adaptor Proteins; D002460:Cell Line; D003598:Cytoskeletal Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012776:Fibroma Virus, Rabbit / Q000276:immunology*; D017930:Genes, Reporter; D006801:Humans; D007155:Immunologic Factors / Q000235:genetics / Q000378:metabolism*; D047468:Immunoprecipitation; D053583:Interleukin-1beta / Q000037:antagonists & inhibitors / Q000235:genetics; D008156:Luciferases / Q000096:biosynthesis / Q000235:genetics; D018613:Microscopy, Confocal; D016328:NF-kappa B / Q000096:biosynthesis / Q000235:genetics; D011485:Protein Binding; D011817:Rabbits; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*
D053468:CARD Signaling Adaptor Proteins; D003598:Cytoskeletal Proteins; D007155:Immunologic Factors; D053583:Interleukin-1beta; D016328:NF-kappa B; C402202:PYCARD protein, human; D014764:Viral Proteins; D008156:Luciferases