[HTML][HTML] Autophagy is an essential component of Drosophila immunity against vesicular stomatitis virus

S Shelly, N Lukinova, S Bambina, A Berman, S Cherry - Immunity, 2009 - cell.com
S Shelly, N Lukinova, S Bambina, A Berman, S Cherry
Immunity, 2009cell.com
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 …
Summary
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.
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