Divergent Roles of Autophagy in Virus Infection

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

In this review we will discuss the current understanding of how virus infection regulates the crosstalk between intracellular signaling and autophagy. Furthermore, we will highlight recent reports on how autophagy exerts its antiviral function and the countermeasures adopted by viruses to exploit and subvert autophagy. Schematic representation of autophagy. The first step in the initiation of mammalian autophagy is the formation of the phagophore, followed by subsequent steps, which include elongation and expansion of the phagophore, closure and completion of a double-membrane autophagosome (which engulfs a portion of the cytoplasm), autophagosome maturation via docking and fusion with endosomal compartments (to form a hybrid vesicular product known as an amphisome) and/or with a lysosome (to form the autolysosome). The inner autophagosomal membrane and cargo is degraded by acid hydrolases inside the autolysosome, and recycling of the resulting macromolecules is mediated via permeases. The molecular machinery regulating autophagy is also depicted. ULK1 and ULK2 complexes that are crucial for induction of autophagy, PI3Kinase-Beclin1 complexes, are required for autophagosome formation, the delivery of membranes to the forming autophagosome is mediated by mammalian Atg9 (mAtg9) and two conjugation systems: LC3-II and Atg12 Atg5 Atg16L complex, which are required during elongation and expansion of the phagophore.