Modulation of influenza A virus replication by microRNA-9 through targeting MCPIP1

MicroRNAs (miRNAs), a family of small non-coding RNAs controlling translation and transcription of its target genes, play important roles in the regulation of various biological processes, including viral infection. Influenza A viruses (IAV) infection alters expression of cellular miRNAs, which in turn can modify the cellular environment to facilitate efficient virus replication. In this study, we showed that IAV infection significantly induced miR-9 expression in A549 cells, which occurred earlier than drastic expression of viral matrix (M) and nucleoprotein (NP) genes. Overexpression of miR-9 enhanced viral gene expression and production of infectious progeny, while knockdown of miR-9 significantly inhibited IAV replication in A549 cells. Recent studies have revealed antiviral potential of monocyte chemoattractant protein 1-induced protein 1 (MCPIP1), a PIN-like RNase capable of targeting and degrading viral RNA. Subsequently, we comprehensively confirmed that MCPIP1 functionally inhibited viral M and NP genes expression and progeny production, and also was regulated by miR-9 in A549 cells. Furthermore, MCPIP1 overexpression abrogated miR-9-induced IAV replication. Taken together, our findings indicate a new role of miR-9 induction in IAV infection and suggest IAV may hijack cellular miR-9 to benefit the viral life cycle. J. Med. Virol. 89:41-48, 2017. © 2016 Wiley Periodicals, Inc.