Role of Glycine Decarboxylase in hepadnaviral infection

B型肝炎病毒是肝硬化和肝细胞癌（HCC）的主要原因。更好地了解病毒的生命周期可能为HBV感染的干预提供靶点，从而降低HBV相关HCC的风险。然而，病毒生命周期的早期阶段和病毒与宿主的相互作用，有助于病毒感染和致病性知之甚少。这421探索性提案的重点是肝DNA病毒相互作用蛋白，p120/甘氨酸脱羧酶的研究。 我们以前发现，p120是一个结合伴侣的禽肝炎B病毒包膜蛋白。它仅在病毒感染组织中表达，其表达水平与细胞对病毒感染的易感性直接相关。它仅在病毒感染组织中表达，其表达水平与细胞对病毒感染的易感性直接相关。此外，尽管野生型的复制能力，但具有消融的p120结合位点的病毒突变体显示出降低的感染性。这些发现表明，p120与病毒生命周期的早期阶段有关。因此，我们计划通过遗传学方法进一步确定其在病毒生命周期中的作用。具体目标#1将确定在分化良好的鸭肝细胞中抑制p120表达或功能是否会降低对病毒感染的易感性。具体目标#2将检查去分化鸭肝细胞中p120的重建是否会恢复生产性病毒感染。此外，我们将确定是否p120是有缺陷的番鸭，鸭种抗嗜肝DNA病毒。我们还将探索通过来自易感北京鸭的p120来恢复病毒感染的可能性。这些研究将提供关于病毒-细胞相互作用的进一步信息，并可能导致开发新的抗病毒策略来预防HBV诱导的肝癌。

Hepatitis B virus is a major cause of liver cirrhosis and hepatocellular carcinoma (HCC). A better understanding of the viral life cycle may provide targets for the intervention of HBV infection, thus reducing the risk of HBV-related HCC. However, the early stages of the viral life cycle and viral-host interactions that contribute to viral infection and pathogenicity are poorly understood. This 421 exploratory proposal focuses on studies on a hepadna virus interacting protein, p120/glycine decarboxylase. We have previous found that p120 is a binding partner of an avian hepatitis B virus envelope protein. It is expressed only in the virus infectable tissues and its expression level is directly correlated with the cellular susceptibility to virus infection. It is expressed only in the virus infectable tissues and its expression level is directly correlated with the cellular susceptibility to virus infection. Moreover, viral mutants with an ablated p120-binding site showed reduced infectivity despite wild-type replication capacity. These findings suggest that p120 is associated with the early stage of the viral life cycle. Therefore, we plan to further establish its role in the viral life cycle by genetic approaches. Specific Aim #1 will determine if inhibition of p120 expression or function in well-differentiated duck hepatocytes will reduce susceptibility to viral infection. Specific Aim #2 will examine whether reconstitution of p120 in de-differentiated duck hepatocytes will restore productive viral infection. In addition, we will determine if p120 is defective in Muscovy ducks, a duck species resistant to hepadnavirus. We will also explore the possibility to restore viral infection by p120 derived from a susceptible Pekin ducks. These studies will provide further information on virus-cell interactions and may lead to development of novel anti-viral strategies for prevention of HBV induced liver cancer.