Cellular microRNA let‐7c inhibits M1 protein expression of the H1N1 influenza A virus in infected human lung epithelial cells

The influenza virus (IV) triggers a series of signalling events inside host cells and induces complex cellular responses. Studies have suggested that host factors play an essential role in IV replication. MicroRNAs (miRNAs) represent a class of small non‐coding RNAs that target mRNAs, triggering either translation repression or RNA degradation. Emerging research suggests that host‐derived cellular miRNAs are involved in mediating the host–IV interaction. Using miRNA microarrays, we identified several miRNAs aberrantly expressed in IV‐infected human lung epithelial cells (A549). Specifically, miR‐let‐7c was highly up‐regulated in IV‐infected A549 cells. PITA and miRanda database screening indicated that the let‐7c seed sequence is a perfect complementary sequence match to the 3′ untranslated region (UTR) of viral gene M1 (+) cRNA, but not to PB2 and PA. As detected by a luciferase reporter system, let‐7c directly targeted the 3′‐UTR of M1 (+) cRNA, but not PB2 and PA. To experimentally identify the function of cellular let‐7c, precursor let‐7c was transfected into A549 cells. Let‐7c down‐regulated IV M1 expression at both the (+) cRNA and protein levels. Furthermore, transfection with a let‐7c inhibitor enhanced the expression of M1. Therefore, let‐7c may reduce IV replication by degrading M1 (+) cRNA. This is the first report indicating that cellular miRNA regulates IV replication through the degradation of viral gene (+) cRNA by matching the 3′‐UTR of the viral cRNA. These findings suggest that let‐7c plays a role in protecting host cells from the virus in addition to its known cellular functions.