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Comparative Study
. 2005 Dec;23(6):587-98.
doi: 10.1016/j.immuni.2005.10.003.

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

James B Johnston  1 , John W Barrett, Steven H Nazarian, Megan Goodwin, Dan Ricciuto, Gen Wang, Grant McFadden
Affiliations
Free article
Comparative Study

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

James B Johnston et al. Immunity. 2005 Dec.
Free article

Erratum in

  • Immunity. 2006 Oct;25(4):687. Ricuttio, Dan [corrected to Ricciuto, Dan]

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.

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Comment in

  • Poxviruses aren't stuPYD.
    Benedict CA, Ware CF. Benedict CA, et al. Immunity. 2005 Dec;23(6):553-5. doi: 10.1016/j.immuni.2005.11.008. Immunity. 2005. PMID: 16356854

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