Beyond self-eating: The control of nonautophagic functions and signaling pathways by autophagy-related proteins

Cadwell, Ken; Debnath, Jayanta

Although we focus on strategies by which viruses coopt ATGs for their own benefit, some viruses are restricted by autophagy. For example, autophagic degradation of ER, reticulophagy, restricts dengue and Zika virus replication on ER-derived membranes. The NS3 protease encoded by these and other flaviviruses counteract this inhibition by cleaving the reticulophagy receptor FAM134B (Lennemann and Coyne, 2017) . Also, multiple herpesviruses encode proteins that bind and inhibit Beclin-1 to avoid autophagy-mediated targeting to the lysosome and antigen presentation to T cells (Deretic and Levine, 2009 ). In other situations, it may be nonautophagic functions of ATGs that determine virulence, as suggested by an siRNA screen comparing the requirement of diverse ATGs during infection by six viruses (Mauthe et al., 2016) . This screen revealed that many of these proteins augment or diminish the replication of individual viruses independent of other ATGs, consistent with the conclusion that nonautophagic functions of ATGs are pervasive during viral infection.