Nondegradative Role of Atg5-Atg12/Atg16L1 Autophagy Protein Complex in Antiviral Activity of Interferon Gamma

被引：208

作者：

Hwang, Seungmin ^{[1
]}

Maloney, Nicole S. ^{[1
]}

Bruinsma, Monique W. ^{[1
]}

Goel, Gautam ^{[3
,4
]}

Duan, Erning ^{[1
]}

Zhang, Lei ^{[1
]}

Shrestha, Bimmi ^{[2
]}

Diamond, Michael S. ^{[2
]}

Dani, Adish ^{[1
]}

Sosnovtsev, Stanislav V. ^{[5
]}

Green, Kim Y. ^{[5
]}

Lopez-Otin, Carlos ^{[6
]}

Xavier, Ramnik J. ^{[3
,4
]}

Thackray, Larissa B. ^{[1
]}

Virgin, Herbert W. ^{[1
]}

机构：

[1] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA

[2] Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA

[3] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA 02114 USA

[4] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA

[5] NIAID, Infect Dis Lab, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA

[6] Univ Oviedo, Inst Univ Oncol, Fac Med, Dept Bioquim & Biol Mol, E-33006 Oviedo, Spain

来源：

CELL HOST & MICROBE | 2012年 / 11卷 / 04期

基金：

美国国家卫生研究院;

关键词：

IMMUNITY; PATHWAY; LC3; REPLICATION; LIPIDATION; ACTIVATION; INFECTION; DISEASE; ABSENCE; INNATE;

D O I：

10.1016/j.chom.2012.03.002

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

Host resistance to viral infection requires type I (alpha/beta) and II (gamma) interferon (IFN) production. Another important defense mechanism is the degradative activity of macroautophagy (herein autophagy), mediated by the coordinated action of evolutionarily conserved autophagy proteins (Atg). We show that the Atg5-Atg12/Atg16L1 protein complex, whose prior known function is in autophagosome formation, is required for IFN gamma-mediated host defense against murine norovirus (MNV) infection. Importantly, the direct antiviral activity of IFN gamma against MNV in macrophages required Atg5-Atg12, Atg7, and Atg16L1, but not induction of autophagy, the degradative activity of lysosomal proteases, fusion of autophagosomes and lysosomes, or the Atg8-processing protein Atg4B. IFN gamma, via Atg5-Atg12/Atg16L1, inhibited formation of the membranous cytoplasmic MNV replication complex, where Atg16L1 localized. Thus, the Atg5-Atg12/Atg16L1 complex performs a pivotal, nondegradative role in IFN gamma-mediated antiviral defense, establishing that multicellular organisms have evolved to use portions of the autophagy pathway machinery in a cassette-like fashion for host defense.

引用

页码：397 / 409

页数：13

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