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, 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.
UR - http://www.scopus.com/inward/record.url?scp=11144324185&partnerID=8YFLogxK
U2 - 10.1038/ni1132
DO - 10.1038/ni1132
M3 - Article
C2 - 15502830
AN - SCOPUS:11144324185
SN - 1529-2908
VL - 5
SP - 1266
EP - 1274
JO - Nature immunology
JF - Nature immunology
IS - 12
ER -