Influenza A Virus NS1 Targets the Ubiquitin Ligase TRIM25 to Evade Recognition by the Host Viral RNA Sensor RIG-I

被引：751

作者：

Gack, Michaela Ulrike ^{[1
,2
,3
,4
]}

Albrecht, Randy Allen ^{[5
]}

Urano, Tomohiko ^{[6
,7
]}

Inn, Kyung-Soo ^{[1
,2
,3
]}

Huang, I-Chueh ^{[2
,3
]}

Carnero, Elena ^{[5
]}

Farzan, Michael ^{[2
,3
]}

Inoue, Satoshi ^{[6
,7
]}

Jung, Jae Ung ^{[1
,2
,3
]}

Garcia-Sastre, Adolfo ^{[5
,8
,9
]}

机构：

[1] Univ So Calif, Keck Sch Med, Dept Mol Microbiol & Immunol, Los Angeles, CA 90033 USA

[2] Harvard Univ, Sch Med, New England Primate Res Ctr, Dept Microbiol & Mol Genet, Southborough, MA 01772 USA

[3] Harvard Univ, Sch Med, New England Primate Res Ctr, Div Tumor Virol, Southborough, MA 01772 USA

[4] Univ Erlangen Nurnberg, Inst Clin & Mol Virol, D-91054 Erlangen, Germany

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

[6] Univ Tokyo, Grad Sch Med, Dept Geriatr Med, Bunkyo Ku, Tokyo 1138655, Japan

[7] Saitama Med Sch, Res Ctr Genom Med, Saitama 3501242, Japan

[8] Mt Sinai Med Ctr, Dept Med, Div Infect Dis, New York, NY 10029 USA

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

来源：

CELL HOST & MICROBE | 2009年 / 5卷 / 05期

关键词：

DOUBLE-STRANDED-RNA; MEDIATED ANTIVIRAL RESPONSES; E4; ORF3; PROTEIN; X-RAY-STRUCTURE; NF-KAPPA-B; RETROVIRAL RESTRICTION; ADAPTER PROTEIN; BETA-INTERFERON; INDUCTION; ACTIVATION;

D O I：

10.1016/j.chom.2009.04.006

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

The ubiquitin ligase TRIM25 mediates Lysine 63-linked ubiquitination of the N-terminal CARD domains of the viral RNA sensor RIG-I to facilitate type I interferon (IFN) production and antiviral immunity. Here, we report that the influenza A virus nonstructural protein 1 (NS1) specifically inhibits TRIM25-mediated RIG-I CARD ubiquitination, thereby suppressing RIG-I signal transduction. A novel domain in NS1 comprising E96/E97 residues mediates its interaction with the coiled-coil domain of TRIM25, thus blocking TRIM25 multimerization and RIG-I CARD domain ubiquitination. Furthermore, a recombinant influenza A virus expressing an E96A/E97A NS1 mutant is defective in blocking TRIM25-mediated antiviral IFN response and loses virulence in mice. Our findings reveal a mechanism by which influenza virus inhibits host IFN response and also emphasize the vital role of TRIM25 in modulating antiviral defenses.

引用

页码：439 / 449

页数：11

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