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Sci Signal. 2015 Dec 8;8(406):ra126. doi: 10.1126/scisignal.aab3183.

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

Author information

1
Laboratory of Immunology, Department of Biological Sciences, Indian Institute of Science Education and Research, Bhopal 462066, India.
2
Pathogenomics Lab, OIE Reference Lab for Avian Influenza, ICAR-National Institute of High Security Animal Diseases, Bhopal 462022, India.
3
Division of Signaling in Cancer and Immunology, Institute for Genetic Medicine, Hokkaido University, Sapporo 060-0815, Japan.
4
Laboratory of Host Defense, WPI Immunology Frontier Research Centre, Osaka University, Osaka 565-0871, Japan.
5
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.

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.

PMID:
26645583
DOI:
10.1126/scisignal.aab3183
[Indexed for MEDLINE]

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