Dengue Virus Inhibition of Autophagic Flux and Dependency of Viral Replication on Proteasomal Degradation of the Autophagy Receptor p62

Metz, P., Chiramel, A., Chatel-Chaix, L., Alvisi, G., Bankhead, P., Mora-Rodriguez, R., Long, G., Hamacher-Brady, A., R. Brady, N., Bartenschlager, R. (2015).

J Virol, 89(15), 8026-8041.

Speaker: Ruei-Yi Chen (陳瑞怡)                                          Time: 15:00~16:00 June 1, 2016

Commentator: Dr. Guey-Chuen Perng (彭貴春老師)          Place: Room 602

Abstract:

Dengue virus (DENV) is a positive-stranded RNA virus of the family Flaviviridae. Our laboratory and others reported that DENV2 infection could induce autophagic progression and cause autophagosome formation, which provides the platform for viral replication. Another report found that DENV induced autophagy could stimulate lipid degradation in the autolysosomes to generate ATP for DENV replication [1]. Autophagic flux is a dynamic process including double membrane autophagosome formation, maturation, fusion with lysosomes and degradation of cytosolic cargoes [2, 3]. The authors developed an ImageStrea image-based, high-content flow-cytometry technique to further dissect DENV induced autophagic flux. They reveal that DENV infection induced autophagic flux and blocked autophagic vesicles degradation during early stage of infection. Furthermore, DENV infection inhibited autophagosome / lysosome fusion at the later stage. In addition, lysosomal activity was induced, but endo-lysosomal trafficking was decreased. The authors further reveal that p62/SQSTM1 restricts DENV replication. The p62 is an autophagy receptor, and plays a crucial role during autophagy elongation process. The p62 protein selectively recruits ubiquitylated proteins into autophagosome for lysosome degradation [4], but DENV infection enhanced proteasomal degradation of p62 to help virus yield. In conclusion, this study reveal that DENV infection altered autophagic flux. It initially activates and later inhibits autophagy. In addition, p62 plays a suppressive role in viral replication.

References:

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4.    Bjorkoy, G., et al., p62/SQSTM1 forms protein aggregates degraded by autophagy and has a protective effect on huntingtin-induced cell death. J Cell Biol, 2005. 171(4): p. 603-14.