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的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 全世界约有4亿HBV慢性携带者，其中每年约有100万人死于肝癌和慢性疾病。丁型肝炎病毒（HDV）的合并或重叠感染可增加肝损伤以及肝硬化和肝细胞癌（HCC）的风险。本研究旨在探讨HBV/HDV感染的分子机制，重点是发病机制。 目的1是了解病毒诱导的发病机制与HBV特定基因型之间的关系。该项目将比较所有已知8种HBV基因型在原代人肝细胞（PHH）中的复制、组装、感染性和宿主应答。拟议的研究将：（i）促进对HBV基因型特异性发病机制的理解;（ii）确定HDV慢性感染是如何维持的;（iii）对理解病毒感染有严重影响。主机交互。最具感染性的HBV基因型的发现将促进：更有效的肽类抗病毒药物的开发;使用PHH体外感染系统的微阵列研究; HBV易感细胞系的建立。 目的2阐明HBV和HDV之间的平衡对感染结局的意义。建议定量研究是什么调节两种病毒在共组装过程中的竞争或稳态。此外，使用PHH，将分析共同感染和超级感染的模式，解决两种病毒是否竞争易感细胞，以及它们的复制率是否相互影响。这些研究将：（i）促进HBV-HDV稳态模型的建立;（ii）增强对与发病机制相关的病毒-病毒相互作用的理解;（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.