Divergent Roles of Autophagy in Virus Infection

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

In the case of coronaviruses, autophagosomes were initially proposed to be sites of RNA replication, since viral replicase proteins colocalized with LC3 and the deletion of Atg5 restricted viral replication [83] . However, subsequent studies suggested that the role of autophagy in viral replication might be a cell type-specific effect [84] . Electron tomography and 3D reconstructions of coronavirus-infected cells demonstrated that DMVs form an adjoining network likely derived from the ER [85] . Moreover, LC3 was localized to the viral replicase machinery, and surprisingly, only unlipidated LC3-I, but not LC3-II, decorated the replication machinery, as well as replication membranes [86] . Furthermore, viral DMVs also stained positive for ER-associated degradation (ERAD) markers. This data suggests that coronaviruses do not require autophagosomes, per se, but utilize components of the autophagy pathway. Another example of viruses utilizing autophagy for viral replication is rotavirus. It was found that the viral protein NS4P, a marker of rotavirus replication sites, colocalized with LC3-positive structures [19] (Figure 4 ). These structures did not stain positive for lamp1, suggesting a block in fusion of virus-associated autophagic structures with lysosomal compartments [19] . However, the precise role of autophagy in viral replication remains to be explored.