MOLECULAR BIOLOGY OF HEPATITIS DELTA VIRUS

肝细胞癌与慢性 B型肝炎病毒（HBV）感染。 预防新发HBV 现在可以通过接种疫苗来实现感染。 但没有 抗病毒治疗可用于对抗慢性乙型肝炎病毒感染， 一旦感染发生。 因此，大量的HBV携带者 患肝细胞癌的风险很高 我们 实验室一直在研究丁型肝炎病毒， 仅感染乙型肝炎病毒携带者。 HDV是一种有缺陷的RNA病毒， 抑制HBV DNA复制。 因此，丁型肝炎病毒与 HBV代表了RNA-DNA相互作用的独特情况。 因此，对丁型肝炎病毒分子生物学的了解和 HDV和HBV之间的相互作用可能为我们提供一个新的 控制HBV复制和减少 肝细胞癌的发病率。 HDV感染频繁 会导致严重的暴发性肝炎 该项目建议使用 表达各种HBV组分的肝癌细胞系， 非肝细胞系研究HDV的分子生物学 HDV和HBV之间的相互作用。 自从HDV 含有环状单链RNA基因组， 动物病毒之间的平行，该项目承诺提供 分子生物学的重要基础信息。 的 将开展以下具体项目：（1）开展RNA 对来自不同地理区域的HDV毒株进行测序， 确定病毒可能的异质性。(2)转染a 将二聚体HDV cDNA导入不同的细胞系，包括肝细胞瘤和 非肝细胞系，以确定HDV RNA的机制 复制和HBV-HDV相互作用。 我们会研究 病毒蛋白质和RNA的合成，以及 病毒颗粒(3)将二聚体RNA转染到不同的细胞系中 来研究RNA加工(4)表达不同的开放式阅读 研究它们可能的基因产物和功能。 这 预计项目将产生关于 在哺乳动物细胞中合成一类新的RNA，并提供 抑制HBV的可能机制，这是主要的 肝细胞癌的病因。

Hepatocellular carcinoma has been causally related to chronic infection by hepatitis B virus (HBV). Prevention of new HBV infection can now be achieved by vaccination. However, no antiviral therapy is available to combat chronic HBV infection, once infection occurs. Thus, the large number of HBV carriers are at a very high risk to hepatocellular carcinoma. Our laboratory has been studying hepatitis delta virus (HDV), which infects only HBV carriers. HDV is a defective RNA virus, but can inhibit HBV DNA replication. Thus, the interactin between HDV and HBV represents a unique case of RNA-DNA interaction. Therefore, the understanding of the molecular biology of HDV and the interaction between HDV and HBV may provide us with a new perspective to the control of HBV replication and reduction of incidence of hepatocellular carcinoma. HDV infection frequently causes severe fulminant hepatitis. This project proposes to use hepatoma cell lines expressing various HBV components and nonhepatic cell lines to study the molecular biology of HDV replication and interaction between HDV and HBV. Since HDV contains a circular single-stranded RNA genome, which has no parallel among animal viruses, this project promises to provide important fundamental information of molecular biology. The following specific projects will be carried out: (1) Perform RNA sequencing of HDV strains from different geographical regions to determine the possible heterogeneity of the virus. (2) Transfect a dimer HDV cDNA into different cell lines, including hepatoma and nonhepatic cell lines to determine the mechanisms of HDV RNA replication and of HBV-HDV interaction. We will examine the synthesis of viral proteins and RNA, and possible production of virus particles. (3) Transfect dimer RNAs into different cell lines to study RNA processing. (4) Express different open reading frames to study their possible gene products and function. This project is expected to yield information on the mechanism of synthesis of a novel class of RNA in mammalian cells, and provide a possible mechanism for inhibition of HBV, which is the major cause of hepatocellualar carcinoma.