IMMUNE REGULATION OF HEPATITIS B VIRUS GENE EXPRESSION

乙肝病毒(乙肝病毒)引起的急性和慢性肝炎是一种主要的 导致肝癌的原因。清除乙肝病毒被认为是由 MHC-I类分子限制细胞毒性T淋巴细胞(CTL)反应。 系统注射乙肝表面抗原CTL，以及IL-2和肿瘤坏死因子α， 非细胞病理性下调小鼠肝脏中HBVRNA的表达 HBs Ag阳性小鼠在转录后水平。这样做的目的是 该项目是通过以下方法确定这种抗病毒作用的分子基础 乙肝病毒特异性CTL可溶性产物激活假说的验证 一种或多种肝细胞效应蛋白(S)，可导致特定的 乙肝病毒转录本的不稳定和/或主动降解。这个 这个项目的具体目标是：1)确定细胞因子或CTL 诱导下调会影响所有的乙肝病毒转录本 转录水平：2)确定乙肝病毒的靶序列(S) S发言全文：对不稳定/降级很重要 在乙肝转基因小鼠中注射细胞因子或CTL；以及，3) 来定义导致特定的细胞内效应分子 乙肝病毒核糖核酸减少。靶序列将通过检测乙肝病毒来确定 体外腐烂对负性调控作用的缺失突变体 用腺病毒载体进行检测和体内实验。我们将会寻找 识别和结合靶序列的肝细胞蛋白 RNA-蛋白质结合实验及一条表达基因的筛选 图书馆。HBVRNA负性调控机制的阐明 表达可能有助于我们理解导致 病毒清除和/或持久性，并可能有助于 抗病毒药物的研究进展 毒品。

Hepatitis B virus (HBV) caused acute and chronic hepatitis and is a major cause of liver cancer. Clearance of HBV is thought to be mediated by the MHC Class I restricted cytotoxic T lymphocyte (CTL) response. Systematically administered HBsAg CTL, as well as IL-2 and TNF alpha, can noncytopathically downregulate HBV RNA expression in the liver of HBsAg positive mice at the post-transcriptional level. The goal of this project is to determine the molecular basis for this antiviral effect by testing the hypothesis that soluble products of HBV specific CTL activate one or more hepatocellular effector protein(s) that cause the specific destabilization and/or the active degradation of HBV transcripts. The specific aims of this project are: 1) to determine if the cytokine or CTL induced downregulation affects all of the HBV transcripts at the post- transcriptional level: 2) to define the target sequence(s) on the HBV S transcript that is (are) important for destabilization/degradation following cytokine or CTL administration in HBV transgenic mice; and, 3) to define the intracellular effector molecules that cause the specific reduction in HBV RNA. The target sequence will be defined by testing HBV deletion mutants for the negative regulatory effect by in vitro decay assays and in vivo using adenovirus vectors. A search will be made for hepatocellular proteins that recognize and bind the target sequence using RNA-protein binding assays and by screening of a cDNA expression library. Elucidation of the mechanisms that negatively regulate HBV RNA expression may contribute to our understanding of the pathways that lead to viral clearance and/or persistence and may be helpful in the development of antiviral drugs.