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, Douglas McFadden

Research output: Contribution to journalArticle

127 Citations (Scopus)

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 (US)
Pages (from-to)1266-1274
Number of pages9
JournalNature Immunology
Volume5
Issue number12
DOIs
StatePublished - Dec 1 2004
Externally publishedYes

Fingerprint

Myxoma virus
Interferon Type I
Extracellular Signal-Regulated MAP Kinases
Virus Diseases
Interferons
Poxviridae Infections
Embryonic Structures
Fibroblasts
Interferon Regulatory Factor-3
STAT1 Transcription Factor
Poxviridae
Rabbits
Infection

ASJC Scopus subject areas

  • Immunology

Cite this

Disruption of Erk-dependent type I interferon induction breaks the myxoma virus species barrier. / Wang, Fuan; Ma, Yiyue; Barrett, John W.; Gao, Xiujuan; Loh, Joy; Barton, Erik; Virgin IV, Herbert W.; McFadden, Douglas.

In: Nature Immunology, Vol. 5, No. 12, 01.12.2004, p. 1266-1274.

Research output: Contribution to journalArticle

Wang, F, Ma, Y, Barrett, JW, Gao, X, Loh, J, Barton, E, Virgin IV, HW & McFadden, D 2004, 'Disruption of Erk-dependent type I interferon induction breaks the myxoma virus species barrier', Nature Immunology, vol. 5, no. 12, pp. 1266-1274. https://doi.org/10.1038/ni1132
Wang, Fuan ; Ma, Yiyue ; Barrett, John W. ; Gao, Xiujuan ; Loh, Joy ; Barton, Erik ; Virgin IV, Herbert W. ; McFadden, Douglas. / Disruption of Erk-dependent type I interferon induction breaks the myxoma virus species barrier. In: Nature Immunology. 2004 ; Vol. 5, No. 12. pp. 1266-1274.
@article{605d26745d9b4efda362ddc252b19a6e,
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 Douglas McFadden",
year = "2004",
month = "12",
day = "1",
doi = "10.1038/ni1132",
language = "English (US)",
volume = "5",
pages = "1266--1274",
journal = "Nature Immunology",
issn = "1529-2908",
publisher = "Nature Publishing Group",
number = "12",

}

TY - JOUR

T1 - Disruption of Erk-dependent type I interferon induction breaks the myxoma virus species barrier

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, Douglas

PY - 2004/12/1

Y1 - 2004/12/1

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.

UR - http://www.scopus.com/inward/record.url?scp=11144324185&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=11144324185&partnerID=8YFLogxK

U2 - 10.1038/ni1132

DO - 10.1038/ni1132

M3 - Article

VL - 5

SP - 1266

EP - 1274

JO - Nature Immunology

JF - Nature Immunology

SN - 1529-2908

IS - 12

ER -