title: Antiviral autophagy restrictsRift Valley fever virus infection and is conserved from flies to mammals.
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.
authors.affiliation: Department of Microbiology, Penn Genome Frontiers Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Ryan H
authors.initials: RH
authors.lastname: Moy
authors.affiliation: Department of Microbiology, Penn Genome Frontiers Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Beth
authors.initials: B
authors.lastname: Gold
authors.affiliation: Department of Microbiology, Penn Genome Frontiers Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Jerome M
authors.initials: JM
authors.lastname: Molleston
authors.affiliation: Department of Microbiology, Penn Genome Frontiers Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Veronica
authors.initials: V
authors.lastname: Schad
authors.affiliation: 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.
authors.forename: Kilangsungla
authors.initials: K
authors.lastname: Yanger
authors.affiliation: Department of Neurology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Mary-Virginia
authors.initials: MV
authors.lastname: Salzano
authors.affiliation: Division of Biological Science, Graduate School of Science, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8602, Japan.
authors.forename: Yoshimasa
authors.initials: Y
authors.lastname: Yagi
authors.affiliation: Division of Infectious Diseases and Immunology, Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.
authors.forename: Katherine A
authors.initials: KA
authors.lastname: Fitzgerald
authors.affiliation: 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.
authors.forename: Ben Z
authors.initials: BZ
authors.lastname: Stanger
authors.affiliation: Department of Neurology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Samantha S
authors.initials: SS
authors.lastname: Soldan
authors.affiliation: 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.
authors.forename: Sara
authors.initials: S
authors.lastname: Cherry
mesh_terms: D000498:Allyl Compounds / Q000494:pharmacology; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology; D001343:Autophagy / Q000187:drug effects / Q000276:immunology*; D002478:Cells, Cultured; D004330:Drosophila; D019143:Evolution, Molecular; D022781:Hepatocytes / Q000187:drug effects / Q000276:immunology / Q000821:virology; D006801:Humans; D017053:Infection Control / Q000379:methods; D008322:Mammals; D051379:Mice; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000276:immunology / Q000821:virology; D011799:Quinazolines / Q000494:pharmacology; D051381:Rats; D012295:Rift Valley Fever / Q000188:drug therapy / Q000276:immunology*; D012296:Rift Valley fever virus / Q000276:immunology*; D051199:Toll-Like Receptor 7 / Q000378:metabolism; D014779:Virus Replication
chemical_list: C560309:6-bromo-4-allylamino-quinazoline; D000498:Allyl Compounds; D000998:Antiviral Agents; D053594:Myeloid Differentiation Factor 88; D011799:Quinazolines; D051199:Toll-Like Receptor 7