Antiviral Autophagy in Drosophila. Jerome M Molleston, Ryan H Moy, Beth Gold, Sara Cherry. Microbiology, Penn Genome Frontiers Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA.

   Autophagy is a highly conserved pathway for degradation of intracellular components and plays a role in immune defense. Our previous studies found that Vesicular Stomatitis virus, an insect-borne virus transmitted to vertebrates, is recognized by a pattern recognition receptor, Toll-7, to induce an antiviral autophagy program in cells and adult flies. Indeed, mutations in Toll-7 or core autophagy components reverts a non-pathogenic infection into a lethal one. This has led us to explore the role of autophagy against additional viruses including Sindbis virus, West Nile virus, and Rift Valley Fever Virus, which represent viruses from the three major families of human arthropod-borne viruses. We are exploring this using genetic and biochemical approaches. We will discuss our findings on the induction of autophagy upon infection and whether autophagy is necessary for control of these viruses. In addition, for those viruses that are restricted by autophagy in insects we are extending our studies to mammalian systems where we are examining whether autophagy may underlie defense against viral infections in across hosts spanning from arthropods to mammals.