Chronic hepatitis B (CHB), which is triggered by hepatitis B virus (HBV) infection, poses a huge health burden on the global community as it is correlated with a significant increasing risk for the development of cirrhosis, liver failure and hepatocellular carcinoma.

Currently the treatment of CHB mainly consists of pegylated interferon (IFN)-α and nucleoside or nucleotide analogs. IFN-α is the first drug licensed to treat HBV infection. In fact, treatment with pegylated IFN results in the highest rate of off-treatment sustained response among currently available drugs, and responses to IFN-based therapy are accompanied by the potential for hepatitis B surface antigen (HBsAg) loss or seroconversion. However, responses to IFN-a therapy vary greatly in CHB patients but underlying mechanisms are almost unknown.

Based on their previous study (Hepatology, 55: 730-741, 2012), Prof. MENG Songdong’s group at the Institute of Microbiology, Chinese Academy of Sciences found that the most abundant liver-specific microRNA (miRNA), miR-122, could be sequestered by mRNAs of IFN-stimulated genes (ISGs), similar to how the miRNA sponge method has been used for miRNA inhibition studies by expressing exogenous sponge RNAs with multiple complementary sites to the miRNA of interest.

The saturation and depletion of miR-122 via binding to at least one ISG-NT5C3 mRNA 3’-UTR increases a target of miR-122, cyclin G1, which may enhance HBV transcription and expression by p53 pathway. Therefore, the down-regulation of miR-122 by INF plays a negative role in IFN-mediated inhibition of HBV replication.

These data may expand the knowledge of how host factors modulate the antiviral efficiency of IFN by multiple mechanisms and provide a rationale for the development of novel therapies that increasing miR-122 may be an effective strategy to enhance anti-HBV efficacy of FN-α.

These results have been published online in Journal of Virology .