The microRNA miR-485 targets host and influenza virus transcripts to regulate antiviral immunity and restrict viral replication

• Published in: Science signaling Vol. 8; no. 406; p. ra126
• Main Authors: Ingle, Harshad, Kumar, Sushil, Raut, Ashwin Ashok, Mishra, Anamika, Kulkarni, Diwakar Dattatraya, Kameyama, Takeshi, Takaoka, Akinori, Akira, Shizuo, Kumar, Himanshu
• Format: Journal Article
• Language: English
• Published: United States 08-12-2015
• Subjects: Animals; DEAD Box Protein 58; DEAD-box RNA Helicases - biosynthesis; DEAD-box RNA Helicases - genetics; DEAD-box RNA Helicases - immunology; Dogs; HEK293 Cells; Humans; Immunity, Innate; Influenza A Virus, H5N1 Subtype - physiology; Influenza, Human - genetics; Influenza, Human - immunology; Influenza, Human - metabolism; Madin Darby Canine Kidney Cells; MicroRNAs - genetics; MicroRNAs - immunology; MicroRNAs - metabolism; Receptors, Immunologic; RNA, Viral - biosynthesis; RNA, Viral - genetics; RNA, Viral - immunology; Signal Transduction - genetics; Signal Transduction - immunology; Viral Proteins - genetics; Viral Proteins - immunology; Viral Proteins - metabolism; Virus Replication - physiology
• ISSN: 1937-9145
• DOI: 10.1126/scisignal.aab3183

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.