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

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

作     者:王海林 颜子颖 侯云德 金冬雁 

作者机构:State Key Laboratory of Molecular Virology and Genetic Engineering Institute of Virology Chinese Academy of Preventive Medicine Beijing 100052 China 

出 版 物:《Science China(Life Sciences)》 (中国科学(生命科学英文版))

年 卷 期:1997年第40卷第6期

页      面:648-656页

核心收录:

学科分类:1001[医学-基础医学(可授医学、理学学位)] 10[医学] 

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 virus Eighth National Five-Year Plan for the Advancement of Medical Science and Technology the St 

主  题:hepatitis C virus (HCV) hepatitis B virus (HBV) core protein gene regulation. 

摘      要: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.

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