病毒与受体互作是HBV研究领域的热点与抗病毒药物开发的重要靶点。Na+/牛磺胆酸共转运多肽（NTCP）介导HBV入侵，然而NTCP是否参与HBV入侵后生活周期尚不清楚。申请人前期研究发现，NTCP显著抑制成熟病毒粒子释放并促进亚病毒颗粒分泌。我们猜测可能是由于细胞内NTCP与病毒蛋白（如L蛋白）相互作用从而影响HBV入侵后生活周期。本项目拟：1）通过转染 HBV复制性质粒确认NTCP参与HBV入侵后生活周期的具体环节；2）通过蛋白互作、干扰NTCP转运等手段明确细胞内NTCP-病毒蛋白互作模式及其亚细胞定位，并阐明NTCP转运对HBV入侵后生活周期的影响；3）通过临床样本分析肝脏NTCP水平与病毒载量的相关性，最终阐明NTCP参与HBV入侵后生活周期的分子机制及其临床相关性。本研究将从新的视角阐明NTCP参与HBV生活周期的新功能，为开发慢性HBV感染治疗药物及治疗策略提供新靶点与新思路。

Interaction between HBV and receptor is research focus and important target for developing antiviral drugs. Na+/taurocholate cotransporting polypeptide (NTCP) mediates HBV entry of hepatocyte, however, it is unknown whether NTCP participates HBV post-entry lifecycle. According to our preliminary data, NTCP was found to inhibit virion release but enhance HBsAg secretion. Hence, we hypothesize that NTCP influenced HBV post-entry lifecycle by intracellular interaction with viral proteins (such as L protein). In this project, we plan to: 1) investigate which step(s) NTCP participates HBV post-entry lifecycle by transfection of HBV-replicating plasmid; 2) confirm protein interactions and their subcellular location, roles of NTCP traffic in HBV post-entry lifecycle by protein-interaction assays, disturbing NTCP traffic et al; 3) try to assess clinical relationship between liver NTCP level and blood HBV copies in HBV patients. This study would uncover new function and mechanism of NTCP in HBV lifecycle, which would provide novel targets for developing anti-HBV drugs and help developing new strategies to treat chronic HBV infection.