Autophagy Protects against Sindbis Virus Infection of the Central Nervous System

Anthony Orvedahl, Sarah MacPherson, Rhea Sumpter, Zsolt Tallóczy, Zhongju Zou, Beth Levine

Research output: Contribution to journalArticle

286 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)115-127
Number of pages13
JournalCell Host and Microbe
Volume7
Issue number2
DOIs
StatePublished - Feb 18 2010

Fingerprint

Sindbis Virus
Autophagy
Virus Diseases
Central Nervous System
Capsid
Viral Proteins
Antiviral Agents
Cell Death
Gene Knockdown Techniques
Neurons
Capsid Proteins
Virus Replication
Genes
Vertebrates
Immunity
Cell Survival
Viruses
Proteins

Keywords

  • MICROBIO
  • MOLIMMUNO
  • MOLNEURO

ASJC Scopus subject areas

  • Immunology and Microbiology(all)
  • Cancer Research
  • Molecular Biology

Cite this

Autophagy Protects against Sindbis Virus Infection of the Central Nervous System. / Orvedahl, Anthony; MacPherson, Sarah; Sumpter, Rhea; Tallóczy, Zsolt; Zou, Zhongju; Levine, Beth.

In: Cell Host and Microbe, Vol. 7, No. 2, 18.02.2010, p. 115-127.

Research output: Contribution to journalArticle

Orvedahl, Anthony ; MacPherson, Sarah ; Sumpter, Rhea ; Tallóczy, Zsolt ; Zou, Zhongju ; Levine, Beth. / Autophagy Protects against Sindbis Virus Infection of the Central Nervous System. In: Cell Host and Microbe. 2010 ; Vol. 7, No. 2. pp. 115-127.
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