Research ArticleHost-Pathogen Interactions

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

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Science Signaling  08 Dec 2015:
Vol. 8, Issue 406, pp. ra126
DOI: 10.1126/scisignal.aab3183

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Targets foreign and domestic

The cytosolic protein RIG-I (retinoic acid–inducible gene I) is a sensor of viral RNA, and its activation induces the host’s antiviral response. Ingle et al. found that infection of various human and mouse cells with RNA viruses, including the H5N1 influenza virus, resulted in the increased production of the microRNA miR-485, which targeted RIG-I mRNA for degradation. As a result, antiviral signaling was inhibited and viral replication was enhanced. However, when cells were exposed to increased amounts of virus, mir-485 was expressed, but viral replication was inhibited. Under these conditions, miR-485 targeted PB1 mRNA, which is a viral transcript required for H5N1 replication. Together, these data suggest that miR-485 exhibits bispecificity, with the extent of infection determining its target.


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.

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