Autophagy protects against Sindbis virus infection of the central nervous system

Autophagy functions in antiviral immunity. However, the ability of endogenous autophagy genes to protect against viral disease in vertebrates remains to be causally established. Here, we report that the autophagy gene Atg5 function is critical for protection against lethal Sindbis virus (SIN) infect...

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Bibliographic Details
Published in:Cell host & microbe 2010-02, Vol.7 (2), p.115-127
Main Authors: Orvedahl, Anthony, MacPherson, Sarah, Sumpter, Jr, Rhea, Tallóczy, Zsolt, Zou, Zhongju, Levine, Beth
Format: Article
Language:English
Subjects:
Alphavirus Infections - immunology
Animals
Apoptosis
Autophagy
Autophagy-Related Protein 5
Cell Line
Central Nervous System - physiology
Mice
Mice, Knockout
Microtubule-Associated Proteins - deficiency
Microtubule-Associated Proteins - physiology
Neurons - pathology
Neurons - virology
Sindbis Virus - immunology
Survival Analysis
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Summary:Autophagy functions in antiviral immunity. However, the ability of endogenous autophagy genes to protect against viral disease in vertebrates remains to be causally established. Here, we report that the autophagy gene Atg5 function is critical for protection against lethal Sindbis virus (SIN) infection of the mouse central nervous system. Inactivating Atg5 in SIN-infected neurons results in delayed clearance of viral proteins, increased accumulation of the cellular p62 adaptor protein, and increased cell death in neurons, but the levels of viral replication remain unaltered. In vitro, p62 interacts with SIN capsid protein, and genetic knockdown of p62 blocks the targeting of viral capsid to autophagosomes. Moreover, p62 or autophagy gene knockdown increases viral capsid accumulation and accelerates virus-induced cell death without affecting virus replication. These results suggest a function for autophagy in mammalian antiviral defense: a cell-autonomous mechanism in which p62 adaptor-mediated autophagic viral protein clearance promotes cell survival.
ISSN:1931-3128
1934-6069
DOI:10.1016/j.chom.2010.01.007