INTERACTION OF HTLV-III/LAV WITH HEPATITIS B VIRUS

获得性免疫缺陷综合征(AIDS)是一种致命的免疫调节 一种混乱，其特征是隐蔽的、定量的和 辅助性/诱导性T细胞亚群功能耗竭。尽管在那里 是牵连人类T细胞白血病/淋巴瘤病毒的确凿证据 (HTLV-III/LAV)作为这种疾病的主要病因，有几个 这种疾病的特征表明，一种或多种传染病病原体 可能在疾病的发展过程中起辅助因素的作用。一种病毒 被认为具有辅因作用的是乙肝病毒。这个 这项提案的长期目标是确定乙肝病毒所扮演的角色 在艾滋病的发展过程中。这项研究的具体目的是 通过全面的分子分析，确定HBVDNA的流行率 感染HTLV-III/LAV的外周血单核细胞(PBMC) 表现出一系列症状的受试者，从轻微和短暂到 严重而持久的疾病。核酸杂交的结果是 PBMC将与现有的乙肝病毒血清标志物(包括 血清相关HBVDNA)和HTLV-III/LAV分离数据。后续行动 对HTLV-III/LAV有抗体的表面健康的献血者将 以确定与PBMC相关的HBVDNA之间的关系 以及疾病的进展。将进行后续评估，以 确定哪个特定单个核细胞亚群(S)包含 将进行乙肝病毒相关DNA和原位杂交，以确定 HBVDNA阳性细胞在各细胞亚群中的百分比(S)。这个 细菌的生理状态、基因组含量和亚细胞定位 与PBMC相关的HBVDNA也将被定义。评估…的水平 病毒基因在HBVDNA阳性单核细胞中的表达 HTLV-III/LAV感染患者的细胞和PBMC将被检查 RNA/DNA杂交法检测乙肝病毒特异性RNA及其放射免疫分析 以及蛋白质印迹技术检测病毒编码抗原的存在。 最后，将尝试建立一个体外模型，使用 共培养和转染法确定乙肝病毒 淋巴样细胞感染可影响复制或细胞病变 HTLV-III/LAV的潜力。建立分子和生物事件 在PBMC内的乙肝病毒复制将是至关重要的 阐明乙肝病毒可能作为一种辅助因子的机制。 HTLV-III诱导的疾病。

The acquired immunodeficiency syndrome (AIDS) is a fatal immunoregulatory disorder which is characterized by an irrevesible, quantitative and functional depletion of the helper/inducer T-cell subset. Although there is substantial evidence to implicate a human T-cell leukemia/lymphoma virus (HTLV-III/LAV) as the primary etiologic agent of this disorder, several characteristics of the disease suggest that one or more infectious agents may function as cofactors in the development of the disease. One virus which has been implicated in a cofactor role is the hepatitis B virus. The long-term objective of this proposal is to define the role which HBV plays in the development of AIDs. The specific aims of this study are to determine, by comprehensive molecular analysis, the prevalence of HBV DNA in peripheral blood mononuclear cells (PBMC) from HTLV-III/LAV infected subjects who display a broad range of symptoms from mild and transient to severe and prolonged disease. The nucleic acid hybridization results in PBMC will be correlated with existing HBV serologic markers (including serum-associated HBV DNA) and with HTLV-III/LAV isolation data. Followup of apparently healthy blood donors, who have antibody to HTLV-III/LAV, will be conducted to determine the relationship between PBMC-associated HBV DNA and the progress of the disease. Subsequent evaluations will be made to determine which specific mononuclear cell subset(s) contains the HBV-related DNA and in situ hybridization will be performed to establish the percentage of HBV DNA positive cells in each cell subset(s). The physical state, genomic content and subcellular localization of PBMC-associated HBV DNA also will be defined. To evaluate the level of viral gene expression which is occurring in HBV DNA positive mononuclear cells, PBMC from HTLV-III/LAV infected patients will be examined for HBV-specific RNA by RNA/DNA hybridization and analyzed by radioimmunoassay and the Western blot technique for the presence of viral-encoded antigens. Finally, an attempt will be made to establish an in vitro model using cocultivation and transfection methodology to determine whether HBV infection of lymphoid cells can influence the replicative or cytopathic potential of HTLV-III/LAV. Establishing the molecular and biologic events of HBV multiplication within PBMC will be of crucial importance in elucidating the mechanism by which HBV may be serving as a cofactor in HTLV-III induced disease.