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PMID: 19362021 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

Autophagy is an essential component of Drosophila immunity against vesicular stomatitis virus.

Immunity ·Vol. 30 ·No. 4 ·2009-04-17 ·Pages 588-98

Shelly S, Lukinova N, Bambina S, Berman A, Cherry S

Abstract

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.

MeSH Terms
Animals Autophagy/immunology Cells, Cultured Drosophila/immunology,virology Fluorescent Antibody Technique Vesiculovirus/immunology,physiology
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Shelly Spencer
Department of Microbiology, Penn Genome Frontiers Institute, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
Lukinova Nina
Bambina Shelly
Berman Allison
Cherry Sara
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Article Info
Journal
Immunity
Abbr.
Immunity
ISSN
1097-4180
DOI
10.1016/j.immuni.2009.02.009
Published
2009-04-17
Epub
2009-00-09
Pages
588-98
Language
English
Region
United States
NLM ID
9432918
PMCID
PMC2754303
Subset
IM
Grants
NIAID NIH HHS · T32 AI007451 · United States
NIAID NIH HHS · 1R01AI07451 · United States
NIAID NIH HHS · T32AI07324 · United States
NIAID NIH HHS · U54AI057168 · United States
NIAID NIH HHS · U54 AI057168 · United States
NIAID NIH HHS · R01 AI074951-01 · United States
NIAID NIH HHS · R01 AI074951 · United States
NIAID NIH HHS · T32 AI007324 · United States
Corrections
CommentIn
PMID: 19371713
External Links
PubMed source DOI: 10.1016/j.immuni.2009.02.009 PMC Full Text View journal details
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