Autophagy is an essential component of Drosophila immunity against vesicular stomatitis virus.
Intrinsic innate immune mechanisms are the first line of defense against pathogens and exist to control infection autonomously in infected cells. Here, we showed that autophagy, an intrinsic mechanism that can degrade cytoplasmic components, played a direct antiviral role against the mammalian viral pathogen vesicular stomatitis virus (VSV) in the model organism Drosophila. We found that the surface glycoprotein, VSV-G, was likely the pathogen-associated molecular pattern (PAMP) that initiated this cell-autonomous response. Once activated, autophagy decreased viral replication, and repression of autophagy led to increased viral replication and pathogenesis in cells and animals. Lastly, we showed that the antiviral response was controlled by the phosphatidylinositol 3-kinase (PI3K)-Akt-signaling pathway, which normally regulates autophagy in response to nutrient availability. Altogether, these data uncover an intrinsic antiviral program that links viral recognition to the evolutionarily conserved nutrient-signaling and autophagy pathways.
Department of Microbiology, Penn Genome Frontiers Institute, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
Spencer
S
Shelly
Nina
N
Lukinova
Shelly
S
Bambina
Allison
A
Berman
Sara
S
Cherry
D000818:Animals; D001343:Autophagy / Q000276:immunology*; D002478:Cells, Cultured; D004330:Drosophila / Q000276:immunology* / Q000821:virology; D005455:Fluorescent Antibody Technique; D018116:Vesiculovirus / Q000276:immunology / Q000502:physiology*