A poxvirus-encoded pyrin domain protein interacts with ASC-1 to inhibit host inflammatory and apoptotic responses to infection.

Abstract	Proinflammatory caspases play an essential role in innate immune responses to infection by regulating the cleavage and activation of proinflammatory cytokines. Activation of these enzymes requires the assembly of an intracellular molecular platform, termed the inflammasome, which is comprised of members of the pyrin domain (PYD)-containing superfamily of apoptosis and inflammation-regulatory proteins. We report here the identification and characterization of a poxvirus-encoded PYD-containing protein that interacts with the ASC-1 component of the inflammasome and inhibits caspase-1 activation and the processing of IL-1beta and IL-18 induced by diverse stimuli. Knockout viruses that do not express this protein are unable to productively infect monocytes and lymphocytes due to an abortive phenotype and are markedly attenuated in susceptible hosts due to decreased virus dissemination and enhanced inflammatory responses at sites of infection. Thus, modulation of inflammasome function constitutes an important immunomodulatory strategy employed by poxviruses to circumvent host antiviral responses.
Authors	James B Johnston, John W Barrett, Steven H Nazarian, Megan Goodwin, Dan Ricciuto, Dan Ricuttio, Gen Wang, Grant McFadden
Journal	Immunity (Immunity) Vol. 23 Issue 6 Pg. 587-98 (Dec 2005) ISSN: 1074-7613 [Print] United States
PMID	16356857 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	CARD Signaling Adaptor Proteins Cytoskeletal Proteins Interleukin-1 Interleukin-18 PYCARD protein, human Viral Proteins Caspase 1
Topics	Amino Acid Sequence Animals Apoptosis (immunology) CARD Signaling Adaptor Proteins Caspase 1 (metabolism) Computational Biology Cytoskeletal Proteins (metabolism) Enzyme Activation (immunology) Fluorescent Antibody Technique, Indirect Humans Immunoblotting Inflammation (immunology, virology) Interleukin-1 (metabolism) Interleukin-18 (metabolism) Microscopy, Fluorescence Models, Immunological Molecular Sequence Data Myxoma virus (genetics, immunology) Rabbits Reverse Transcriptase Polymerase Chain Reaction Sequence Alignment Viral Proteins (genetics, immunology, metabolism)

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