Molecular Basis of Cytokine-Induced Clearance of HBV DNA

描述：(改编自调查人员摘要)：乙肝病毒(乙肝病毒)可以在感染者中确定慢性或急性感染。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转归中起重要作用，但由细胞因子干扰素α/β、干扰素γ和肿瘤坏死因子α介导的非细胞溶解机制也强烈地抑制了乙肝病毒的复制和基因表达。细胞因子介导的对乙肝病毒复制的抑制对于清除病毒，同时保护肝脏免受CTL介导的广泛损伤至关重要。尽管已证实细胞因子对病毒复制的抑制发生在病毒前基因组RNA衣壳的组装或稳定水平，但这一过程发生的机制和涉及的细胞蛋白尚未确定。这项建议的重点是确定以细胞因子调节的方式与乙肝病毒核心抗原相互作用的细胞蛋白，并确定这些相互作用与清除感染细胞中的乙肝病毒复制中间体的相关性。

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.