| First Author | Hwang S | Year | 2012 |
| Journal | Cell Host Microbe | Volume | 11 |
| Issue | 4 | Pages | 397-409 |
| PubMed ID | 22520467 | Mgi Jnum | J:236442 |
| Mgi Id | MGI:5806053 | Doi | 10.1016/j.chom.2012.03.002 |
| Citation | Hwang S, et al. (2012) Nondegradative role of Atg5-Atg12/ Atg16L1 autophagy protein complex in antiviral activity of interferon gamma. Cell Host Microbe 11(4):397-409 |
| abstractText | 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 IFNgamma-mediated host defense against murine norovirus (MNV) infection. Importantly, the direct antiviral activity of IFNgamma 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. IFNgamma, 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 IFNgamma-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. |
