HEPATITIS B VIRUS/HEPATITIS DELTA VIRUS INFECTION, ITS RELATION TO PATHOGENESIS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 全球约有4亿慢性乙肝病毒携带者，其中每年约有100万人死于肝癌和慢性病。合并或重叠感染丁型肝炎病毒(HDV)会增加肝脏损伤，并增加患肝硬变和肝细胞癌(HCC)的风险。本研究旨在探讨乙型肝炎病毒/丁型肝炎病毒感染的分子机制，重点探讨其发病机制。 目标1的目标是了解病毒诱导的致病机制与特定的乙肝病毒基因型之间的关系。该项目将比较所有已知的8种乙肝病毒基因型在原代人类肝细胞(PHH)中的复制、组装、传染性和宿主反应。建议的研究将：(I)促进对HBV型特异性致病机制的了解；(Ii)确定HDV慢性感染是如何维持的；(Iii)对了解病毒与宿主的相互作用产生严重影响。最具传染性的乙肝病毒基因的发现将有助于：开发更有效的多肽抗病毒药物；利用PHH体外感染系统进行微阵列研究；建立对乙肝病毒敏感的细胞系。 目的2阐明乙肝病毒和丁型肝炎病毒之间的平衡对感染结局的意义。建议定量检查在共同组装过程中是什么调节了两种病毒之间的竞争或动态平衡。此外，利用PHH，将分析联合感染和超级感染的模式，以解决这两种病毒是否竞争敏感细胞，以及它们的复制率是否相互影响。这些研究将有助于：(I)促进建立HBVHDV动态平衡的模型；(Ii)增进对病毒-病毒相互作用与发病机制的了解；(Iii)阐明慢性感染的机制。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. There are approximately 400 million of HBV chronic carriers worldwide, of whom about 1 million die annually from liver cancer and chronic disease. Co- or super-infection with hepatitis delta virus (HDV) can increase liver damage and risk of cirrhosis and hepatocellular carcinoma (HCC). This proposal is aimed to ascertain molecular mechanism of HBV/HDV infection with emphasis on pathogenesis. The goal of Aim 1 is to understand relationship between virus-induced pathogenesis and a particular genotype of HBV. The project will compare replication, assembly, infectivity in primary human hepatocytes (PHH) and host response for all known 8 HBV genotypes. The studies proposed will: (i) facilitate understanding of the HBV genotype-specific pathogenesis; (ii) ascertain how HDV chronic infection is maintained; (iii) have a serious impact on understanding of virushost interactions. The finding of the most infectious HBV genotype will facilitate: development of more potent peptide antivirals; microarray studies using the system of in vitro infection of PHH; establishment of HBV-susceptible cell lines. Aim 2 will delineate significance of the balance between HBV and HDV for outcome of infection. It is proposed to quantitatively examine what regulates competition or homeostasis between the two viruses during co-assembly. Also, using PHH, the patterns of co- and super-infection will be analyzed, addressing if the two viruses compete for susceptible cells, and if their replication rates are mutually affected. These studies will: (i) facilitate building the model of HBV-HDV homeostasis; (ii) enhance understanding of virus-virus interactions in relation to pathogenesis; (iii) clarify the mechanism of chronic infection.