夏宇尘，现为武汉大学基础医学院教授，博导，病毒学国家重点实验室PI，国家“千人计划”青年项目入选者。主要研究成果在Science, Gastroenterology, Journal of Hepatology, Journal of Virology等学术期刊以第一作者发表，其中两篇一作文章入选ESI高被引论文。现为国际肝癌协会会员、欧洲肝病协会会员。 担任Gastroenterology, Hepatology, eLIFE, Journal of Virology，Antiviral Research等杂志审稿人。
通讯作者
连展扬（T. Jake Liang），M.D，美国医学院院士，现任美国国立卫生研究院NIDDK转化研究副主任，肝病教研室主任。哈佛大学本科毕业后，进入哈佛医学院获得医学博士学位。连展扬是国际知名的病毒性肝炎和肝脏疾病领域的领导者，有300多篇科学论文发表在高影响力的期刊上，包括NEJM，Science，Nature，Nature Medicine， Science Trans Med，Nature Genetics，Ann Med of Int Med，J Clin Invest等，并参与编写多本学术著作。连展扬曾担任Gastroenterology副主编（IF 20）（1996-2001,2016-2021），Hepatology（IF 14）（2001-2006）和 Gut（IF 18）（2014-2017）。他1996当选为美国临床医学研究会会士，2002年当选美国医师协会会士和 2016年当选美国国家医学院院士，2017年当选美国科学促进会（AAAS）会士。他在许多学术界都很活跃 专业协会，包括ASCI，美国肝脏研究协会（AASLD）和美国胃肠病学协会（AGA）。曾担任AASLD主席。
ABSTRACT
Hepatitis B virus (HBV) infection is a major health problem worldwide, and chronically infected individuals are at high risk of developing cirrhosis and hepatocellular carcinoma (HCC). The molecular mechanisms whereby HBV causes HCC are largely unknown. Using a biologically relevant system of HBV infection of primary human hepatocytes (PHHs), we studied how HBV perturbs gene expression and signaling pathways of infected hepatocytes and whether these effects are relevant to productive HBV infection and HBV-associated HCC. Using a human growth factor antibody array, we first showed that HBV infection induced a distinct profile of growth factor production by PHHs, marked particularly by significantly lower levels of the transforming growth factor β (TGF-β) family of proteins in the supernatant. Transcriptome profiling next revealed multiple changes in cell proliferation and cell cycle control pathways in response to HBV infection. A human cell cycle PCR array validated deregulation of more than 20 genes associated with the cell cycle in HBV-infected PHHs. Cell cycle analysis demonstrated that HBV-infected PHHs are enriched in the G2/M phase compared to the predominantly G0/G1 phase of cultured PHHs. HBV proviral host factors, such as PPARA, RXRA, and CEBPB, were upregulated upon HBV infection and particularly enriched in cells in the G2/M phase. Together, these results support the notion that HBV deregulates cell cycle control to render a cellular environment that is favorable for productive HBV infection. By perturbing cell cycle regulation of infected cells, HBV may coincidently induce a premalignant phenotype that predisposes infected hepatocytes to subsequent malignant transformation.
IMPORTANCE
Hepatitis B virus (HBV) infection is a major health problem with high risk of developing hepatocellular carcinoma (HCC). By using a biologically relevant system of HBV infection of primary human hepatocytes (PHHs), we studied how HBV perturbs gene expression and whether these effects are relevant to HBV-associated HCC. HBV induced a distinct profile of growth factor production, marked particularly by significantly lower levels of the transforming growth factor β(TGF-β) family of proteins. Transcriptome profiling revealed multiple changes in cell proliferation and cell cycle control pathways. Cell cycle analysis demonstrated that HBV-infected PHHs are enriched in the G2/M phase. HBV proviral host factors were upregulated upon infection and particularly enriched in cells in the G2/M phase. Together, these results support the notion that HBV deregulates cell cycle control to render a cellular environment that is favorable for productive infection. This may coincidently induce a
premalignant phenotype that predisposes infected hepatocytes to subsequent malignant transformation.