Antiviral autophagy restrictsRift Valley fever virus infection and is conserved from flies to mammals
Department of Medicine, Division of Infectious Diseases and Immunology
Allyl Compounds; Animals; Antiviral Agents; Autophagy; Cells, Cultured; Drosophila; Evolution, Molecular; Hepatocytes; Humans; Infection Control; Mammals; Mice; Myeloid Differentiation Factor 88; Neurons; Quinazolines; Rats; Rift Valley Fever; Rift Valley fever virus; Toll-Like Receptor 7; Virus Replication
Cells | Immunity | Immunology and Infectious Disease | Immunology of Infectious Disease | Infectious Disease | Parasitic Diseases | Virus Diseases | Viruses
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.
DOI of Published Version
Immunity. 2014 Jan 16;40(1):51-65. doi: 10.1016/j.immuni.2013.10.020. Epub 2013 Dec 26. Link to article on publisher's site
Moy, Ryan H.; Gold, Beth; Molleston, Jerome M.; Schad, Veronica; Yanger, Kilangsungla; Salzano, Mary-Virginia; Yagi, Yoshimasa; Fitzgerald, Katherine A.; Stanger, Ben Z.; Soldan, Samantha S.; and Cherry, Sara, "Antiviral autophagy restrictsRift Valley fever virus infection and is conserved from flies to mammals" (2014). Infectious Diseases and Immunology Publications and Presentations. 186.