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 con-taining the 5&...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 con-taining the 5' noncoding (5'NC) and the core regions have been isolated from Chinese HBV- and HCV-coinfected pa-tients. Sequence comparison and phylogenetic analysis showed that the HCV sequence cloned from coinfected individu-als is indistinguishable from that identified in other patients. Cotransfection assay confirmed that the core protein ex-pressed 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.展开更多
基金This work is partly supported by grant 85-916-01-03 (1990-1994) to Jin Dong-Yan for the development of diagnostic reagents for the infection of hepatitis C virusEighth National Five-Year Plan for the Advancement of Medical Science and Technologythe St
文摘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 con-taining the 5' noncoding (5'NC) and the core regions have been isolated from Chinese HBV- and HCV-coinfected pa-tients. Sequence comparison and phylogenetic analysis showed that the HCV sequence cloned from coinfected individu-als is indistinguishable from that identified in other patients. Cotransfection assay confirmed that the core protein ex-pressed 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.
