Characterization of MicroRNA Expression Profiles Associated with Hepatitis B Virus Replication and Clearance in Vivo and in Vitro

Background And Aim: Alpha interferon (IFN-α) is an approved treatment for chronic hepatitis B (CHB). MicroRNA (miRNA) are currently known as a part of IFN-mediated antiviral defense. We aimed at characterizing the miRNA expression associated with hepatitis B virus (HBV) replication and IFN-mediated HBV clearance.

Methods: We investigated the expression patterns of cellular miRNA induced by HBV replication and/or IFN-α treatment in HepG2 cells, and also analyzed the miRNA response in peripheral blood mononuclear cells in CHB patients on IFN-α treatment. The differentially expressed miRNA were verified using quantitative real-time polymerase chain reaction and an miRNA expression pattern was classified based on the final virological response.

Results: A total of 223 miRNA were differentially expressed (> 1.5 folds) between the HepG2.2.15 and HepG2 cells, including 24 highly differentially expressed miRNA (> 5 folds). With 12 h of IFN-α treatment, 23 totally differentially expressed miRNA were identified in HepG2 cells; whereas only five miRNA were identified in HepG2.2.15 cells. Similar amounts of the miRNA were regulated in patients with HBeAg or non-HBeAg seroconversion; whereas levels of eight miRNA were significantly differentially expressed between the two groups.

Conclusions: HBV replication alters miRNA expression profiles and impairs IFN-inducible miRNA response in HepG2 cells. The miRNA expression pattern of peripheral blood mononuclear cells in CHB patients with IFN therapy can be associated with their therapeutic outcome.