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

Fuan Wang, Yiyue Ma, John W. Barrett, Xiujuan Gao, Joy Loh, Erik Barton, Herbert W. Virgin IV, Grant McFadden

Research output: Contribution to journalArticle

134 Scopus citations

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.

Original languageEnglish
Pages (from-to)1266-1274
Number of pages9
JournalNature immunology
Volume5
Issue number12
DOIs
StatePublished - Dec 1 2004

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    Wang, F., Ma, Y., Barrett, J. W., Gao, X., Loh, J., Barton, E., Virgin IV, H. W., & McFadden, G. (2004). Disruption of Erk-dependent type I interferon induction breaks the myxoma virus species barrier. Nature immunology, 5(12), 1266-1274. https://doi.org/10.1038/ni1132