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

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DOIResolve DOI: http://doi.org/10.1016/j.immuni.2005.10.003
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TypeArticle
Journal titleImmunity (Cambridge, Mass.)
ISSN10747613
1074-7613
Volume23
IssueDecember 6
Pages587598; # of pages: 12
Subjectpoxvirus; pyrin; ASC-1; protein; apoptotic responses; infection
AbstractProinflammatory 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-1ß 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.
Publication date
PublisherElsevier
Copyright noticeYou may reproduce (print, make photocopies, or download) materials from NPArC without permission for non-commercial purposes (research, education, and private study), on the condition that you provide proper attribution of the sources in all copies.
LanguageEnglish
AffiliationNRC Institute for Nutrisciences and Health (INH-ISNS); National Research Council Canada
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public
Peer reviewedYes
NRC publication
This is a non-NRC publication

"Non-NRC publications" are publications authored by NRC employees prior to their employment by NRC.

NPARC number9126866
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Record identifier17bb19e6-dd1f-4954-a956-3e32ef91eaf2
Record created2009-10-03
Record modified2016-05-09
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