Divergent Roles of Autophagy in Virus Infection

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

The role of SLRs in the selective autophagic degradation of viruses was recently studied in the context of Sindbis virus infection [37] . Orvedahl and co-workers found that autophagic degradation of Sindbis virus involves the selective degradation of the viral capsid in a p62-dependent manner ( Figure 3 ). The precise signal for capsid recognition by p62 is unclear, but is independent of ubiquitin association, because neurons of infected wild-type or Atg5-/-mice did not contain accumulations of ubiquitinated cellular or viral proteins [37] . Moreover, in an effort to identify host cell factors that target Sindbis virus and HSV-1 for autophagic degradation, the authors performed a genome-wide RNA interference screen. Surprisingly, this screen identified common molecular determinants involved in the targeting of viral nucleocapsids and mitochondria for autophagic degradation [62] . This virophagy and mitophagy is critically determined by SMURF1, an E3 ubiquitin ligase that acts as a bona fide mediator of selective autophagy [62] . SMURF1 might therefore be considered as a novel SLR specifically involved in controlling viral infections. Whether SMURF1 is also involved in autophagy of bacterial invaders remains to be determined.