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Immunity. 2014 Jan 16;40(1):51-65. doi: 10.1016/j.immuni.2013.10.020. Epub 2013 Dec 26.

Antiviral autophagy restrictsRift Valley fever virus infection and is conserved from flies to mammals.

Author information

1
Department of Microbiology, Penn Genome Frontiers Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
2
Abramson Family Cancer Research Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA; Division of Gastroenterology, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
3
Department of Neurology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
4
Division of Biological Science, Graduate School of Science, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8602, Japan.
5
Division of Infectious Diseases and Immunology, Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.
6
Department of Microbiology, Penn Genome Frontiers Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: cherrys@mail.med.upenn.edu.

Abstract

Autophagy has been implicated as a component of host defense, but the significance of antimicrobial autophagy in vivo and the mechanism by which it is regulated during infection are poorly defined. Here we found that antiviral autophagy was conserved in flies and mammals during infection with Rift Valley fever virus (RVFV), a mosquito-borne virus that causes disease in humans and livestock. In Drosophila, Toll-7 limited RVFV replication and mortality through activation of autophagy. RVFV infection also elicited autophagy in mouse and human cells, and viral replication was increased in the absence of autophagy genes. The mammalian Toll-like receptor adaptor, MyD88, was required for anti-RVFV autophagy, revealing an evolutionarily conserved requirement for pattern-recognition receptors in antiviral autophagy. Pharmacologic activation of autophagy inhibited RVFV infection in mammalian cells, including primary hepatocytes and neurons. Thus, autophagy modulation might be an effective strategy for treating RVFV infection, which lacks approved vaccines and therapeutics.

PMID:
24374193
PMCID:
PMC3951734
DOI:
10.1016/j.immuni.2013.10.020
[Indexed for MEDLINE]
Free PMC Article

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