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乙肝病毒感染的分子机制

乙肝病毒感染的分子机制
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  • 批准号:81525018
  • 批准年度: 2015年
  • 学科分类:病毒、病毒感染与宿主免疫(H1904) |
  • 项目负责人:李文辉
  • 负责人职称:研究员
  • 依托单位:北京生命科学研究所
  • 资助金额:350万元
  • 项目类别:国家杰出青年科学基金
  • 研究期限:2016年01月01日 至 2020年12月31日
  • 中文关键词: 乙肝病毒;感染
  • 英文关键词:Hepatitis B virus;viral receptor;HBV infection;HBsAg;viral infection factors

项目摘要

中文摘要

李文辉以乙型肝炎病毒(Hepatitis B virus,HBV)为主要研究对象,取得了重要进展。发现介导人HBV及其卫星病毒HDV特异性感染肝脏实质细胞的受体分子为:钠离子-牛磺胆酸共转运蛋白(sodium taurocholate cotransporting polypeptide, NTCP)。阐明了在病毒侵入细胞水平,NTCP限制HBV/HDV对小鼠等感染的重要种属特异性决定位点;发现HBV/HDV病毒感染与NTCP转运胆酸的生理作用相互影响,病毒蛋白与胆酸在NTCP上作用部位重叠,但与受体分子的作用机制有所不同;证明人NTCP转基因鼠能支持HDV的体内感染。发现HBV受体NTCP回答了HBV感染领域内一个关键的科学问题,为乙肝病毒基础和应用研究打开了新的大门,被认为是乙肝病毒研究领域的重大突破。李文辉还曾于2003年发现SARS病毒的细胞受体是血管紧张素转换酶2 (ACE2)。

英文摘要

My primary research interest is to understand the molecular mechanisms of viral infection. During the past several years, my lab at National Institute of Biological Sciences has been working on viral entry of hepatitis B virus (HBV). We have made clear and substantial progresses in understanding viral infection of HBV and its satellite virus hepatitis D virus (HDV)..We identified that NTCP (sodium taurocholate cotransporting polypeptide), a bile acids transporter predominantly expressed in liver, as a functional receptor for HBV and HDV. The finding opens a new door for understanding HBV/HDV infection. NTCP complemented human hepatoma HepG2 cells have become a valuable culture system for studying HBV/HDV infection and developing novel drugs against the viral infection. We examined the contribution of NTCP for determining the species specificity of HBV and HDV at entry level, and we were the first to demonstrate that two regions on NTCP largely determine HBV species at entry, although additional binding sites for HBV in NTCP may also be needed. We studied NTCP-mediated HBV and HDV infection in relation to NTCP’s physiological function. The results suggested that viral entry of hepatitis B and D viruses and bile salts transportation share common molecular determinants on NTCP, however the viruses might be transported by NTCP via a mechanism distinct to that of bile acid transporting. Lately, we confirmed that mice expressing human NTCP (hNTCP-Tg) in liver support bona fade HDV infection. The hNTCP-Tg mouse model provides a convenient platform for studying HDV infection and evaluating HDV and HBV viral entry inhibitors in vivo..Our discovery of NTCP as a cellular receptor for HBV and HDV and the extended in-depth studies answered some critical and long-standing questions in the research field of HBV infection. The work has been well-recognized and the receptor discovery is regarded as a milestone in HBV research. .Back to year 2003, working as a postdoctoral fellow at Harvard Medical School, I discovered that angiotensin-converting enzyme 2 (ACE2) is a cellular receptor for SARS-Coronavirus.

评估说明

    国家自然科学基金项目“乙肝病毒感染的分子机制”发布于爱科学iikx,并永久归类于相关科学基金导航中,仅供广大科研工作者查询、学习、选题参考。国科金是根据国家发展科学技术的方针、政策和规划,以及科学技术发展方向,面向全国资助基础研究和应用研究,发挥着促进我国基础研究源头创新的作用。国科金的真正价值在于它能否为科学进步和社会发展带来积极的影响。

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