Role of Glycine Decarboxylase in hepadnaviral infection

甘氨酸脱羧酶在肝炎病毒感染中的作用

• 批准号: 6466437
• 负责人: Jisu Li
• 金额: $ 15.4万
• 依托单位: RHODE ISLAND HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-04-01 至 2004-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6466437
• 关键词: Adenoviridae; RNA; antisense nucleic acid; decarboxylases; enzyme activity; glycine; hepatitis B virus group; host organism interaction; liver cells; microorganism culture; recombinant virus; virus diseases; virus infection mechanism; virus protein; virus replication

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.

乙型肝炎病毒是肝硬化和肝细胞癌（HCC）的主要病因。更好地了解病毒生命周期可能为干预HBV感染提供靶点，从而降低HBV相关HCC的风险。然而，人们对病毒生命周期的早期阶段以及导致病毒感染和致病性的病毒-宿主相互作用知之甚少。这个421的探索性提议侧重于肝病毒相互作用蛋白p120/甘氨酸脱羧酶的研究。我们之前已经发现p120是禽乙型肝炎病毒包膜蛋白的结合伙伴。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，切除p120结合位点的病毒突变体尽管具有野生型复制能力，但感染性降低。这些发现表明p120与病毒生命周期的早期阶段有关。因此，我们计划通过遗传学方法进一步确定其在病毒生命周期中的作用。特异性目的1将确定抑制p120在分化良好的鸭肝细胞中的表达或功能是否会降低对病毒感染的易感性。特异性目标#2将研究p120在去分化鸭肝细胞中的重组是否会恢复生产性病毒感染。此外，我们将确定p120在番鸭中是否存在缺陷，番鸭是一种对肝炎病毒有抵抗力的鸭。我们还将探索从易感北京鸭中提取的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HBV诱导的肝癌。