Role of Glycine Decarboxylase in hepadnaviral infection

乙肝病毒是引起肝硬变和肝细胞癌的主要原因。更好地了解病毒生命周期可能为干预乙肝病毒感染提供靶点，从而降低与乙肝病毒相关的肝细胞癌的风险。然而，导致病毒感染和致病性的病毒生命周期的早期阶段和病毒与宿主的相互作用却知之甚少。这份421的探索性提案侧重于对庚型肝炎病毒相互作用蛋白p120/甘氨酸脱羧酶的研究。我们已经发现，p120是一种禽类乙肝病毒包膜蛋白的结合伙伴。它只在病毒感染的组织中表达，其表达水平与细胞对病毒感染的易感性直接相关。它只在病毒感染的组织中表达，其表达水平与细胞对病毒感染的易感性直接相关。此外，尽管具有野生型复制能力，但具有p120结合位点的病毒突变体显示出感染性降低。这些发现表明，p120与病毒生命周期的早期阶段有关。因此，我们计划通过基因方法进一步确定其在病毒生命周期中的作用。具体目标#1将确定抑制分化良好的鸭肝细胞中p120的表达或功能是否会降低对病毒感染的易感性。具体目标#2将检查去分化的鸭肝细胞中p120的重组是否将恢复生产性病毒感染。此外，我们将确定p120在番鸭身上是否存在缺陷，这是一种对庚型核糖核酸病毒具有抵抗力的鸭种。我们还将探索通过来自易感北京鸭的p120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乙肝病毒诱导的肝癌。

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.