李文辉的人物成就

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研究概述Research Description

本实验室的主要研究兴趣为囊膜病毒侵入细胞及相关过程的分子机制。病毒侵入细胞起始于与细胞表面受体的结合。围绕这一过程，我们希望探索：病毒细胞受体分子的识别；病毒受体是如何介导病毒感染的；其它胞内因子是如何参与病毒侵入的；病毒蛋白是如何进行免疫逃逸的；如何有效地抑制病毒的感染，等。我们综合运用病毒学，生物化学，化学生物学等多学科方法，以回答上述问题。这些研究将有利于深化对于病毒基本生物学，及病毒与感染宿主相互作用的认识与理解，并且有助于开发有效的抗病毒制剂及新型疫苗。

乙型肝炎是危害人类健康的严重传染病，是导致肝硬化、肝癌的重要病因。我们最近成功地发现并确认了人类乙型肝炎病毒，及其密切相关的丁型肝炎病毒感染肝细胞所必需的功能受体分子是肝细胞膜上的钠离子-牛磺胆酸-协同转运蛋白（NTCP）。这一重要发现为进一步深入研究乙肝病毒及相关致病机制打开了新的大门，并为研发新的药物和治疗手段提供了可能。

Our lab tries to understand the entry mechanisms of enveloped viruses. Regardless of the type of enveloped virus, the initial step of viral entry always involves the interactions between the viral envelope protein(s) and viral receptor(s) on host cells. The questions that we are mostly interested in are: what is the specific cellular receptor for a virus? How does the receptor contribute to viral entry? How does the viral entry protein evade the host immune response? How can viral infection be inhibited by entry inhibitor or host immunity. We seek to identify the receptors and elucidate the entry processes of viral pathogens important to human health. Knowledge of viral entry mechanisms will deepen our understanding of basic biology of viruses and their host cells, and offer new opportunities to develop more efficient inhibitors against the infections and new generation of viral vaccines.

Hepatitis B virus (HBV) infection and its associated cirrhosis and hepatocellular carcinoma cause about one million deaths annually. The molecular mechanisms by which HBV and its satellite virus Hepatitis D virus (HDV) infect human liver have been elusive. By taking state-of-the-art affinity purification approach, we recently identified sodium taurocholate cotransporting polypeptide (NTCP), a liver bile acid transporter, as a specific receptor for HBV and HDV. NTCP binds to a critical receptor binding region of viral envelope L protein and contributes substantially to the efficiency of HBV and HDV infections. This finding advances our understanding of the HBV and HDV infection and may lead to new strategies for prevention and treatment of these viral infections and associated diseases.

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