RESUMEN

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.

Asunto(s)

Inmunidad Innata , Subtipo H5N1 del Virus de la Influenza A/fisiología , Gripe Humana/metabolismo , MicroARNs/metabolismo , ARN Viral/biosíntesis , Replicación Viral/fisiología , Animales , Proteína 58 DEAD Box , ARN Helicasas DEAD-box/biosíntesis , ARN Helicasas DEAD-box/genética , ARN Helicasas DEAD-box/inmunología , Perros , Células HEK293 , Humanos , Gripe Humana/genética , Gripe Humana/inmunología , Células de Riñón Canino Madin Darby , MicroARNs/genética , MicroARNs/inmunología , ARN Viral/genética , ARN Viral/inmunología , Receptores Inmunológicos , Transducción de Señal/genética , Transducción de Señal/inmunología , Proteínas Virales/genética , Proteínas Virales/inmunología , Proteínas Virales/metabolismo