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

Seungmin Hwang, Nicole S. Maloney, Monique W. Bruinsma, Gautam Goel, Erning Duan, Lei Zhang, Bimmi Shrestha, Michael S. Diamond, Adish Dani, Stanislav V. Sosnovtsev, Kim Y. Green, Carlos Lopez-Otin, Ramnik J. Xavier, Larissa B. Thackray, Herbert W. Virgin

Research output: Contribution to journalArticle

141 Scopus citations

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.

Original languageEnglish
Pages (from-to)397-409
Number of pages13
JournalCell Host and Microbe
Volume11
Issue number4
DOIs
StatePublished - Apr 19 2012

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    Hwang, S., Maloney, N. S., Bruinsma, M. W., Goel, G., Duan, E., Zhang, L., Shrestha, B., Diamond, M. S., Dani, A., Sosnovtsev, S. V., Green, K. Y., Lopez-Otin, C., Xavier, R. J., Thackray, L. B., & Virgin, H. W. (2012). Nondegradative role of Atg5-Atg12/Atg16L1 autophagy protein complex in antiviral activity of interferon gamma. Cell Host and Microbe, 11(4), 397-409. https://doi.org/10.1016/j.chom.2012.03.002