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

doi:10.1038/ni1132

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 journal › Article › peer-review

151 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 language	English (US)
Pages (from-to)	1266-1274
Number of pages	9
Journal	Nature Immunology
Volume	5
Issue number	12
DOIs	https://doi.org/10.1038/ni1132
State	Published - Dec 2004
Externally published	Yes

ASJC Scopus subject areas

Immunology and Allergy
Immunology

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title = "Disruption of Erk-dependent type I interferon induction breaks the myxoma virus species barrier",

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.",

author = "Fuan Wang and Yiyue Ma and Barrett, {John W.} and Xiujuan Gao and Joy Loh and Erik Barton and {Virgin IV}, {Herbert W.} and Grant McFadden",

note = "Funding Information: We thank R. Schreiber, G. Stark, H. Nguyen, A. Koromilas, D. Frank, R. Silverman, B. Williams, J. Ihle, M. Aguet, K. Mossman and D. Barber for their advice and reagents, which helped in the development of this project, and D. Hall for help with the manuscript. Supported by the Canadian Institutes of Health Research.",

year = "2004",

month = dec,

doi = "10.1038/ni1132",

language = "English (US)",

volume = "5",

pages = "1266--1274",

journal = "Nature Immunology",

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AU - Wang, Fuan

AU - Ma, Yiyue

AU - Barrett, John W.

AU - Gao, Xiujuan

AU - Loh, Joy

AU - Barton, Erik

AU - Virgin IV, Herbert W.

AU - McFadden, Grant

N1 - Funding Information: We thank R. Schreiber, G. Stark, H. Nguyen, A. Koromilas, D. Frank, R. Silverman, B. Williams, J. Ihle, M. Aguet, K. Mossman and D. Barber for their advice and reagents, which helped in the development of this project, and D. Hall for help with the manuscript. Supported by the Canadian Institutes of Health Research.

PY - 2004/12

Y1 - 2004/12

N2 - 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.

AB - 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.

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

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