title: Japanese encephalitis virus activates autophagy as a viral immune evasion strategy.
abstract: In addition to manipulating cellular homeostasis and survivability, autophagy also plays a crucial role in numerous viral infections. In this study, we discover that Japanese encephalitis virus (JEV) infection results in the accumulation of microtubule-associated protein 1 light chain 3-II (LC3-II) protein and GFP-LC3 puncta in vitro and an increase in autophagosomes/autolysosomes in vivo. The fusion between autophagosomes and lysosomes is essential for virus replication. Knockdown of autophagy-related genes reduced JEV replication in vitro, as indicated by viral RNA and protein levels. We also note that JEV infection in autophagy-impaired cells displayed active caspases cleavage and cell death. Moreover, we find that JEV induces higher type I interferon (IFN) activation in cells deficient in autophagy-related genes as the cells exhibited increased phosphorylation and dimerization of interferon regulatory factor 3 (IRF3) and mitochondrial antiviral signaling protein (MAVS) aggregation. Finally, we find that autophagy is indispensable for efficient JEV replication even in an IFN-defective background. Overall, our studies provide the first description of the mechanism of the autophagic innate immune signaling pathway during JEV infection.
authors: State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, Hubei, China.
authors: Rui
authors: R
authors: Jin
authors: Wandi
authors: W
authors: Zhu
authors: Shengbo
authors: S
authors: Cao
authors: Rui
authors: R
authors: Chen
authors: Hui
authors: H
authors: Jin
authors: Yang
authors: Y
authors: Liu
authors: Shaobo
authors: S
authors: Wang
authors: Wei
authors: W
authors: Wang
authors: Gengfu
authors: G
authors: Xiao
mesh_terms: D000818:Animals; D001343:Autophagy / Q000276:immunology*; D002460:Cell Line; D002470:Cell Survival / Q000276:immunology; D006224:Cricetinae; D004664:Encephalitis Virus, Japanese / Q000276:immunology* / Q000472:pathogenicity*; D004672:Encephalitis, Japanese / Q000276:immunology / Q000473:pathology / Q000821:virology; D054884:Host-Pathogen Interactions / Q000276:immunology; D006801:Humans; D057131:Immune Evasion; D007370:Interferon Type I / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D015398:Signal Transduction / Q000276:immunology; D014775:Virus Activation / Q000276:immunology*; D014779:Virus Replication / Q000276:immunology
chemical_list: D007370:Interferon Type I