Divergent Roles of Autophagy in Virus Infection

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

Organisms have developed highly complex defense networks against invading pathogens, and in turn, pathogens either disable or manipulate host defenses to hijack their host and eventually to co-exist with it. As described in this review, autophagy fits into this theme, because on one hand, it can promote viral replication; on the other hand, it contributes to innate and adaptive immunity and thus, limits pathogen replication. Obviously as a result of co-evolution, viruses developed multiple strategies to evade autophagy or more extremely to reverse the antiviral effects of autophagy into proviral ones. In spite of the tremendous progress made in the last couple of years, many important aspects remain to be addressed. For instance, autophagy selectively degrades viruses, but can viruses induce autophagy to selectively degrade antiviral platforms like mitochondria or peroxisomes? Such events are plausible considering the mitochondrial or peroxisomal localization of essential innate signaling molecules, such as MAVS (mitochondrial antiviral-signaling protein) or TRIF [92, 93] . Another important question relates to selective autophagy. This process requires cargo-binding adaptor proteins, which all have a molecular signature interaction with LC3 in order to feed bound cargo to the autophagosome. Since viruses can also induce selective autophagy, it will be important to investigate if viral proteins can directly bind LC3 and whether this interaction is LIR dependent. Studies of these and many other aspects will certainly foster our understanding to the pathogen-host interaction, but might also open new avenues for the development of novel prophylactic or therapeutic antiviral strategies.