Divergent Roles of Autophagy in Virus Infection

Chiramel, Abhilash I.; Brady, Nathan R.; Bartenschlager, Ralf

As alluded to in the previous section, the direct contribution of autophagy to promoting HCV replication is discussed controversially. However, two recent studies provided insights as to how autophagy might promote HCV replication indirectly, namely by blocking the innate immune response. The study by Ke and Chen demonstrated that UPR induced by HCV activates the complete autophagy pathway, which is required for efficient viral replication [36] . Importantly, this enhancement of replication correlated with suppression of innate antiviral immunity. Interestingly, the analogous activation of UPR and inhibition of IFNarguing that both viruses utilize the same strategy to maximize RNA replication and to suppress the innate antiviral defense (Figure 4 ). In agreement with these conclusions, Shrivastava and coworkers found that gene silencing of Beclin 1 and Atg7 in immortalized human hepatocytes not only reduced HCV RNA replication, but also resulted in the activation of IFN signaling [82] . These studies reveal a novel mechanism employed by HCV and DENV to evade an anti-viral innate immune response.