Human micro RNA hsa‐mi R ‐1231 suppresses hepatitis B virus replication by targeting core m RNA

Summary Pathogen‐specific mi RNA profiles might reveal potential new avenues for therapy. To identify mi RNA s directly associated with hepatitis B virus ( HBV ) in hepatocytes, we performed a mi RNA array analysis using urokinase‐type plasminogen activator (u PA )–severe combined immunodeficiency ( SCID ) mice where the livers were highly repopulated with human hepatocytes and human immune cells are absent. Mice were inoculated with HBV ‐infected patient serum samples. Eight weeks after HBV infection, human hepatocytes were collected from liver tissues, and mi RNA s were analysed using the T oray 3 D array system. The effect of mi RNA s on HBV replication was analysed using HBV ‐transfected H ep G 2 cells. Four mi RNA s, hsa‐mi R ‐486‐3p, hsa‐mi R ‐1908, hsa‐mi R ‐675 and hsa‐mi R ‐1231 were upregulated in mouse and human livers with HBV infection. These mi RNA s were associated with immune response pathways such as inflammation mediated by chemokine and cytokine signalling. Of these mi RNA s, hsa‐mi R ‐1231, which showed high homology with HBV core and HB x sequences, was most highly upregulated. In HBV ‐transfected H ep G 2 cells, overexpression of hsa‐mi R ‐1231 resulted in suppression of HBV replication with HBV core reduction. In conclusion, a novel interaction between hsa‐mi R ‐1231 and HBV replication was identified. This interaction might be useful in developing new therapeutic strategies against HBV .