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PMID: 22520467 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Nondegradative role of Atg5-Atg12/ Atg16L1 autophagy protein complex in antiviral activity of interferon gamma.

Cell host & microbe ·Vol. 11 ·No. 4 ·2012-04-19 ·Pages 397-409

Hwang S, Maloney NS, Bruinsma MW, Goel G, Duan E, Zhang L, Shrestha B, Diamond MS, Dani A, Sosnovtsev SV, Green KY, Lopez-Otin C, Xavier RJ, Thackray LB, Virgin HW

Abstract

Host resistance to viral infection requires type I (α/β) and II (γ) 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 IFNγ-mediated host defense against murine norovirus (MNV) infection. Importantly, the direct antiviral activity of IFNγ 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. IFNγ, 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 IFNγ-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.

MeSH Terms
Animals Autophagy Autophagy-Related Protein 12 Autophagy-Related Protein 5 Autophagy-Related Proteins Caliciviridae Infections/genetics,immunology,metabolism Carrier Proteins/genetics,metabolism Humans Interferon-gamma/immunology Mice Mice, Knockout Microtubule-Associated Proteins/genetics,metabolism Norovirus/physiology Protein Binding Proteins/genetics,metabolism
Chemicals
Atg12 protein, mouse Atg16l1 protein, mouse Atg5 protein, mouse Autophagy-Related Protein 12 Autophagy-Related Protein 5 Autophagy-Related Proteins Carrier Proteins Microtubule-Associated Proteins Proteins Interferon-gamma
Authors & Affiliations
15 authors, click to expand affiliations / ORCID
Hwang Seungmin
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Maloney Nicole S
Bruinsma Monique W
Goel Gautam
Duan Erning
Zhang Lei
Shrestha Bimmi
Diamond Michael S
Dani Adish
Sosnovtsev Stanislav V
Green Kim Y
Lopez-Otin Carlos
Xavier Ramnik J
Thackray Larissa B
Virgin Herbert W
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Article Info
Journal
Cell host & microbe
Abbr.
Cell Host Microbe
ISSN
1934-6069
DOI
10.1016/j.chom.2012.03.002
Published
2012-04-19
Pages
397-409
Language
English
Region
United States
NLM ID
101302316
PMCID
PMC3348177
Subset
IM
Grants
NIAID NIH HHS · R01 AI084887 · United States
NIAID NIH HHS · R01 AI065982 · United States
NIDDK NIH HHS · P30 DK043351 · United States
NIAID NIH HHS · U54 AI057160-07 · United States
NCRR NIH HHS · UL1 RR024992 · United States
NIAMS NIH HHS · P30 AR048335 · United States
NCI NIH HHS · P30 CA091842 · United States
NCI NIH HHS · R01 CA096511-07 · United States
NIAID NIH HHS · U54 AI057160 · United States
NCI NIH HHS · R01 CA096511 · United States
NIAID NIH HHS · R01 AI054483-06A1 · United States
NIAID NIH HHS · R01 AI084887-04 · United States
NIAID NIH HHS · R01 AI054483 · United States
External Links
PubMed source DOI: 10.1016/j.chom.2012.03.002 PMC Full Text View journal details
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