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Hepatitis B virus (HBV) infection is the leading cause of liver diseases. However, the molecular mechanisms of HBV infection and carcinogenesis have not been fully elucidated. In this study, we found that cyclin D2 was upregualted in HBV-expressing cells and liver tissues of HBV-transgenic mice. Gene silencing of cyclin D2 inhibited HBV DNA replicative intermediates, 3.5 kb mRNA, core protein level, as well as the secretions of HBsAg and HBeAg. On the contrary, overexpression of cyclin D2 promoted HBV replication. Furthermore, cyclin D2 regulated HBV replication by enhancing the activity of HBV core and Sp1 promoters by targeting transcription factor CREB2. Silencing of CREB2 abolished enhancement of HBV replication induced by cyclin D2. Together, our study has uncovered a positive role of cyclin D2 in HBV replication. It is conceivable that therapeutic application of cyclin D2 inhibitor in HBV infection therapy. [ABSTRACT FROM AUTHOR]

Chronic hepatitis B virus (HBV) infection is a major risk factor for liver cirrhosis and hepatocellular carcinoma. Nevertheless, the molecular mechanism of HBV replication remains elusive. SIRT1 is a class III histone deacetylase that is a structure component of the HBV cccDNA minichromosome. In this study, we found by using microarray-based gene expression profiling analysis that SIRT1 was upregulated in HBV-expressing cells. Gene silencing of SIRT1 significantly inhibited HBV DNA replicative intermediates, 3.5-kb mRNA, and core protein levels. In contrast, the overexpression of SIRT1 augmented HBV replication. Furthermore, SIRT1 enhanced the activity of HBV core promoter by targeting transcription factor AP-1. The c-Jun subunit of AP-1 was bound to the HBV core promoter region, as demonstrated by using a chromatin immunoprecipitation assay. Mutation of AP-1 binding site or knockdown of AP-1 abolished the effect of SIRT1 on HBV replication. Finally, SIRT1 inhibitor sirtinol also suppressed the HBV DNA replicative intermediate, as well as 3.5-kb mRNA. Our study identified a novel host factor, SIRT1, which may facilitate HBV replication in hepatocytes. These data suggest a rationale for the use of SIRT1 inhibitor in the treatment of HBV infection. [ABSTRACT FROM AUTHOR]