title: The microRNA miR-485 targets host and influenza virus transcripts to regulate antiviral immunity and restrict viral replication.
abstract: MicroRNAs (miRNAs) are small noncoding RNAs that are responsible for dynamic changes in gene expression, and some regulate innate antiviral responses. Retinoic acid-inducible gene I (RIG-I) is a cytosolic sensor of viral RNA; RIG-I activation induces an antiviral immune response. We found that miR-485 of the host was produced in response to viral infection and targeted RIG-I mRNA for degradation, which led to suppression of the antiviral response and enhanced viral replication. Thus, inhibition of the expression of mir-485 markedly reduced the replication of Newcastle disease virus (NDV) and the H5N1 strain of influenza virus in mammalian cells. Unexpectedly, miR-485 also bound to the H5N1 gene PB1 (which encodes an RNA polymerase required for viral replication) in a sequence-specific manner, thereby inhibiting replication of the H5N1 virus. Furthermore, miR-485 exhibited bispecificity, targeting RIG-I in cells with a low abundance of H5N1 virus and targeting PB1 in cells with increased amounts of the H5N1 virus. These findings highlight the dual role of miR-485 in preventing spurious activation of antiviral signaling and restricting influenza virus infection.
authors.affiliation: Laboratory of Immunology, Department of Biological Sciences, Indian Institute of Science Education and Research, Bhopal 462066, India.
authors.forename: Harshad
authors.initials: H
authors.lastname: Ingle
authors.affiliation: Laboratory of Immunology, Department of Biological Sciences, Indian Institute of Science Education and Research, Bhopal 462066, India.
authors.forename: Sushil
authors.initials: S
authors.lastname: Kumar
authors.affiliation: Pathogenomics Lab, OIE Reference Lab for Avian Influenza, ICAR-National Institute of High Security Animal Diseases, Bhopal 462022, India.
authors.forename: Ashwin Ashok
authors.initials: AA
authors.lastname: Raut
authors.affiliation: Pathogenomics Lab, OIE Reference Lab for Avian Influenza, ICAR-National Institute of High Security Animal Diseases, Bhopal 462022, India.
authors.forename: Anamika
authors.initials: A
authors.lastname: Mishra
authors.affiliation: Pathogenomics Lab, OIE Reference Lab for Avian Influenza, ICAR-National Institute of High Security Animal Diseases, Bhopal 462022, India.
authors.forename: Diwakar Dattatraya
authors.initials: DD
authors.lastname: Kulkarni
authors.affiliation: Division of Signaling in Cancer and Immunology, Institute for Genetic Medicine, Hokkaido University, Sapporo 060-0815, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kameyama
authors.affiliation: Division of Signaling in Cancer and Immunology, Institute for Genetic Medicine, Hokkaido University, Sapporo 060-0815, Japan.
authors.forename: Akinori
authors.initials: A
authors.lastname: Takaoka
authors.affiliation: Laboratory of Host Defense, WPI Immunology Frontier Research Centre, Osaka University, Osaka 565-0871, Japan.
authors.forename: Shizuo
authors.initials: S
authors.lastname: Akira
authors.affiliation: Laboratory of Immunology, Department of Biological Sciences, Indian Institute of Science Education and Research, Bhopal 462066, India. Laboratory of Host Defense, WPI Immunology Frontier Research Centre, Osaka University, Osaka 565-0871, Japan.
authors.forename: Himanshu
authors.initials: H
authors.lastname: Kumar
mesh_terms: D000818:Animals; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D004285:Dogs; D057809:HEK293 Cells; D006801:Humans; D007113:Immunity, Innate; D053124:Influenza A Virus, H5N1 Subtype / Q000502:physiology*; D007251:Influenza, Human / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D061985:Madin Darby Canine Kidney Cells; D035683:MicroRNAs / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D012367:RNA, Viral / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D011971:Receptors, Immunologic; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D014764:Viral Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D014779:Virus Replication / Q000502:physiology*
chemical_list: C556501:MIRN485 microRNA, human; D035683:MicroRNAs; D012367:RNA, Viral; D011971:Receptors, Immunologic; D014764:Viral Proteins; C077346:influenza virus polymerase basic protein 1; C452820:RIGI protein, human; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases