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Nat Immunol. 2004 Dec;5(12):1266-74. Epub 2004 Oct 24.

Disruption of Erk-dependent type I interferon induction breaks the myxoma virus species barrier.

Author information

1
Robarts Research Institute, and Department of Microbiology and Immunology, The University of Western Ontario, London, Ontario N6G 2V4, Canada.

Abstract

Myxoma virus, a member of the poxvirus family, causes lethal infection only in rabbits, but the mechanism underlying the strict myxoma virus species barrier is not known. Here we show that myxoma virus infection of primary mouse embryo fibroblasts elicited extracellular signal-regulated kinase (Erk) signaling, which was integrated to interferon regulatory factor 3 activation and type I interferon induction. We further show that Erk inactivation or disruption of interferon signaling mediated by the transcription factor STAT1 broke the cellular blockade to myxoma virus multiplication. Moreover, STAT1 deficiency rendered mice highly susceptible to lethal myxoma virus infection. Thus, the Erk-interferon-STAT1 signaling cascade elicited by myxoma virus in nonpermissive primary mouse embryo fibroblasts mediates an innate cellular barrier to poxvirus infection.

PMID:
15502830
DOI:
10.1038/ni1132
[Indexed for MEDLINE]
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