Mouse STAT2 Restricts Early Dengue Virus Replication

被引：173

作者：

Ashour, Joseph ^{[1
]}

Morrison, Juliet ^{[1
]}

Laurent-Rolle, Maudry ^{[1
]}

Belicha-Villanueva, Alan ^{[1
]}

Plumlee, Courtney Ray ^{[5
]}

Bernal-Rubio, Dabeiba ^{[1
]}

Williams, Katherine L. ^{[4
]}

Harris, Eva ^{[4
]}

Fernandez-Sesma, Ana ^{[1
,2
,3
]}

Schindler, Christian ^{[5
]}

Garcia-Sastre, Adolfo ^{[1
,2
,3
]}

机构：

[1] Mt Sinai Sch Med, Dept Microbiol, New York, NY 10029 USA

[2] Mt Sinai Sch Med, Dept Med, Div Infect Dis, New York, NY 10029 USA

[3] Mt Sinai Sch Med, Global Hlth & Emerging Pathogens Inst, New York, NY 10029 USA

[4] Univ Calif Berkeley, Sch Publ Hlth, Div Infect Dis & Vaccinol, Berkeley, CA 94720 USA

[5] Columbia Univ, Dept Microbiol & Immunol, New York, NY 10032 USA

来源：

CELL HOST & MICROBE | 2010年 / 8卷 / 05期

基金：

美国国家卫生研究院;

关键词：

V-PROTEIN; ALPHA/BETA-INTERFERON; SIGNAL TRANSDUCER; IMMUNE-RESPONSE; NS5; PROTEIN; INFECTION; MICE; INHIBITION; DISEASE; MODEL;

D O I：

10.1016/j.chom.2010.10.007

中图分类号：

Q93 [微生物学];

学科分类号：

071005 [微生物学];

摘要：

Dengue virus encodes several interferon antagonists. Among these the NS5 protein binds STAT2, a necessary component of the type I interferon signaling pathway, and targets it for degradation. We now demonstrate that the ability of dengue NS5 to associate with and degrade STAT2 is species specific. Thus, NS5 is able to bind and degrade human STAT2, but not mouse STAT2. This difference was exploited to demonstrate, absent manipulation of the viral genome, that NS5-mediated IFN antagonism is essential for efficient virus replication. Moreover, we demonstrate that differences in NS5 mediated binding and degradation between human and mouse STAT2 maps to a region within the STAT2 coiled-coil domain. By using STAT2(-/-) mice, we also demonstrate that mouse STAT2 restricts early dengue virus replication in vivo. These results suggest that overcoming this restriction through transgenic mouse technology may help in the development of a long-sought immune-competent mouse model of dengue virus infection.

引用

页码：410 / 421

页数：12

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