Molecular characterization of suppression of hepatitis B virus transcription by hepatitis C virus core protein

To further elucidate the molecular mechanisms underlying the suppression of hepatitis B virus (HBV) expression by the hepatitis C virus (HCV) core protein, five molecular clones of HCV cDNA sequence containing the 5' noncoding (5'NC) and the core regions have been isolated from Chinese HBV-and HCV-coinfected patients. Sequence comparison and phylogenetic analysis showed that the HCV sequence cloned from coinfected individuals is indistinguishable from that identified in other patients. Cotransfection assay confirmed that the core protein expressed from one of the cloned sequence is capable of suppressing the expression of hepatitis B surface and e antigens (HBsAg and HBeAg, respectively). Deletion mapping revealed that the C-terminal hydrophobic region of the HCV core is necessary for the suppression. Results from reporter assays demonstrated that HCV core protein interacts with the HBV C promoter and enhancer II elements and down-regulates the transcription of HBV as well as other cellular and heterologous viral genes in both hepatic and non-hepatic cell lines. Taken together, the findings suggest HCV core protein as a multifunctional negative regulator of transcription critically involved in the molecular interactions between HBV and HCV, and between HCV and the cell.