Molecular Basis of Cytokine-Induced Clearance of HBV DNA

细胞因子诱导 HBV DNA 清除的分子基础

• 批准号: 6511378
• 负责人: MICHAEL ROBEK
• 金额: $ 3.83万
• 依托单位: SCRIPPS RESEARCH INSTITUTE, THE
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-06-23 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6511378
• 关键词: cytokine; genetic library; genetically modified animals; hepatitis B antigens; hepatitis B virus group; host organism interaction; interferon gamma; laboratory mouse; liver cells; microorganism immunology; protein protein interaction; tumor necrosis factor alpha; virus DNA; yeast two hybrid system

DESCRIPTION: (Adapted from the Investigator's abstract): Hepatitis B Virus (HBV) can establish either a chronic or acute infection in infected individuals. Although cytotoxic T-lymphocyte (CTL)-mediated killing of infected hepatocytes likely plays an important role in the outcome of infection, HBV replication and gene expression are also strongly inhibited by non-cytolytic mechanisms mediated by the cytokines interferon alpha/beta, interferon gamma, and tumor necrosis factor alpha. The cytokine-mediated inhibition of HBV replication is likely to be critically important for clearance of the virus while protecting the liver from extensive CTLmediated damage. Although it has been demonstrated that the cytokine-mediated inhibition of HBV replication occurs at the level of assembly or stability of viral pre-genomic RNA-containing capsids, the mechanism by which this process occurs and the cellular proteins involved have not been determined. The focus of this proposal is to identify cellular proteins that interact with HBV core antigen in a cytokine-regulated manner, and to determine the relevance of these interactions to the clearance of HBV replicative intermediates from infected cells.

产品说明：（改编自研究者摘要）：B型肝炎病毒（HBV）可在受感染个体中建立慢性或急性感染。尽管细胞毒性T淋巴细胞（CTL）介导的对感染肝细胞的杀伤可能在感染的结果中起重要作用，但HBV复制和基因表达也受到细胞因子干扰素α/β、干扰素γ和肿瘤坏死因子α介导的非细胞溶解机制的强烈抑制。苦参碱介导的HBV复制抑制可能对清除病毒至关重要，同时保护肝脏免受广泛的CTL介导的损伤。尽管已经证明，在病毒前基因组RNA-含有衣壳的组装或稳定性水平上，马槟榔碱介导的HBV复制抑制发生，但该过程发生的机制和涉及的细胞蛋白尚未确定。该建议的重点是确定细胞蛋白质相互作用的HBV核心抗原在一个鸟嘌呤调节的方式，并确定这些相互作用的相关性，从感染的细胞清除HBV复制中间体。