Divergent Roles of Autophagy in Virus Infection

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

Conflicting reports have been published as to the role of autophagy for the HCV replication cycle [23, 26, 79, 80] . For instance, Sir and co-workers used the highly permissive cell clone Huh 7.5 and found that transfection of HCV RNA induces autophagic vacuoles and leads to an incomplete autophagic process that promotes viral replication [23] . Dreux and co-workers employed Huh7 cells infected with HCV and found that autophagy was only required for initiating the translation of incoming viral RNA, but not for establishment or maintenance of viral replication [26] . Moreover, in Huh7 cells containing HCV replicons of different genotypes (1a, 1b or 2a), the knock down of Atg proteins did not affect expression of viral proteins [81] . In contrast, in another study that employed Huh7.5 cells, the knock-down of Atg7 dramatically decreased production of HCV particles, but did not affect viral replication [80] . Moreover, a recent report showed that knock-down of the autophagy-related proteins beclin 1 (BCN1) and Atg7 inhibited HCV replication in immortalized human hepatocytes (IHHs) [82] . These conflicting results might be due to the use of different cell lines. In fact, a recent study highlighted the importance of the UPR and autophagy during HCV infection and demonstrated that autophagy enhances HCV replication by inhibiting an innate immune response [36] . Since Huh7 clones differ in their capability to mount an innate antiviral defense, the use of different cell lines could explain, at least in part, the contradictory results.