title: MOV10 Provides Antiviral Activity against RNA Viruses by Enhancing RIG-I-MAVS-Independent IFN Induction.
abstract: Moloney leukemia virus 10, homolog (MOV10) is an IFN-inducible RNA helicase, associated with small RNA-induced silencing. In this article, we report that MOV10 exhibits antiviral activity, independent of its helicase function, against a number of positive- and negative-strand RNA viruses by enhancing type I IFN induction. Using a number of genome-edited knockout human cells, we show that IFN regulatory factor 3-mediated IFN induction and downstream IFN signaling through IFN receptor was necessary to inhibit virus replication by MOV10. MOV10 enhanced IFN regulatory factor 3-mediated transcription of IFN. However, this IFN induction by MOV10 was unique and independent of the known retinoic acid-inducible gene I/mitochondrial antiviral-signaling protein-mediated RNA-sensing pathway. Upon virus infection, MOV10 specifically required inhibitor of κB kinase ε, not TANK-binding kinase 1, for its antiviral activity. The important role of MOV10 in mediating antiviral signaling was further supported by the finding that viral proteases from picornavirus family specifically targeted MOV10 as a possible innate immune evasion mechanism. These results establish MOV10, an evolutionary conserved protein involved in RNA silencing, as an antiviral gene against RNA viruses that uses an retinoic acid-inducible gene I-like receptor-independent pathway to enhance IFN response.
authors.affiliation: Cancer Virology Program, University of Pittsburgh Cancer Institute, Pittsburgh, PA 15213; Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213; and.
authors.forename: Rolando A
authors.initials: RA
authors.lastname: Cuevas
authors.affiliation: Cancer Virology Program, University of Pittsburgh Cancer Institute, Pittsburgh, PA 15213; Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213; and.
authors.forename: Arundhati
authors.initials: A
authors.lastname: Ghosh
authors.affiliation: Institute for Clinical Chemistry and Clinical Pharmacology, University of Bonn, 53105 Bonn, Germany.
authors.forename: Christina
authors.identifier: 0000-0002-8095-6111
authors.initials: C
authors.lastname: Wallerath
authors.affiliation: Institute for Clinical Chemistry and Clinical Pharmacology, University of Bonn, 53105 Bonn, Germany.
authors.forename: Veit
authors.initials: V
authors.lastname: Hornung
authors.affiliation: Cancer Virology Program, University of Pittsburgh Cancer Institute, Pittsburgh, PA 15213; Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213; and.
authors.forename: Carolyn B
authors.identifier: 0000-0002-1884-6309
authors.initials: CB
authors.lastname: Coyne
authors.affiliation: Cancer Virology Program, University of Pittsburgh Cancer Institute, Pittsburgh, PA 15213; Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213; and saumen@pitt.edu.
authors.forename: Saumendra N
authors.identifier: 0000-0002-2850-6121
authors.initials: SN
authors.lastname: Sarkar
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D018188:Cardiovirus Infections / Q000276:immunology*; D004686:Encephalomyocarditis virus / Q000276:immunology*; D055785:Gene Knockdown Techniques; D057809:HEK293 Cells; D006801:Humans; D057131:Immune Evasion; D007113:Immunity, Innate; D050838:Interferon Regulatory Factor-3 / Q000378:metabolism; D007370:Interferon Type I / Q000378:metabolism; D020365:RNA Helicases / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D012367:RNA, Viral / Q000235:genetics; D018168:Receptors, Retinoic Acid / Q000378:metabolism; D018353:Rhabdoviridae Infections / Q000276:immunology*; D015398:Signal Transduction; D014721:Vesicular stomatitis Indiana virus / Q000276:immunology*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C494232:IRF3 protein, human; D050838:Interferon Regulatory Factor-3; D007370:Interferon Type I; C505371:MAVS protein, human; C437968:PLAAT4 protein, human; D012367:RNA, Viral; D018168:Receptors, Retinoic Acid; C530476:Mov10 protein, human; D020365:RNA Helicases