Divergent Roles of Autophagy in Virus Infection

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

The first report demonstrating that autophagy can be involved in delivering PAMPs or viral nucleic acids to endosomal TLRs comes from the study of VSV-infected plasmacytoid dendritic cells (pDCs) [55] ( Figure 3) . The authors showed that the production of interferon---infected pDCs depended on the autophagic delivery of viral replication intermediates to TLR7 present on late endosomes. This activation of IFNtreatment of VSV-infected pDCs with Wortmannin or 3-methyladenine (3-MA) that both inhibit Vps34 activity, IFN--/-mice exhibited a similar phenotype and carried higher viral loads, suggesting that autophagy is important in controlling VSV replication in vivo. However, the exact mechanism by which viral PAMPs are selectively targeted by autophagosomes to the TLR-resident late endosomal compartment remains to be determined.