INTERACTION OF HTLV-III/LAV WITH HEPATITIS B VIRUS

获得性免疫缺陷综合征（艾滋病）是一种致命的免疫调节性疾病， 疾病的特点是一个不可逆的，定量的， 辅助/诱导T细胞亚群的功能性耗竭。 虽然 是人类T细胞白血病/淋巴瘤病毒 （HTLV-III/LAV）作为这种疾病的主要病原体， 疾病的特征表明，一种或多种感染因子 可能在疾病的发展中起辅助因子的作用。 一种病毒 参与辅因子作用的是B型肝炎病毒。 的 该提案的长期目标是确定HBV所起的作用 艾滋病的发展。 本研究的具体目的是 通过综合分子分析确定HBV DNA的患病率 在来自HTLV-III/LAV感染的外周血单核细胞（PBMC）中， 受试者表现出从轻度和短暂到 严重和长期的疾病。 核酸杂交导致 PBMC将与现有的HBV血清学标志物（包括 血清相关HBV DNA）和HTLV-III/LAV分离数据。 后续行动 有HTLV-III/LAV抗体的表面健康献血者， 以确定PBMC相关的HBV DNA与 以及疾病的进展。 随后将进行评价， 确定哪个特定的单核细胞亚群含有 将进行HBV相关DNA和原位杂交，以确定 每个细胞亚群中HBV DNA阳性细胞的百分比。 的 物理状态、基因组含量和亚细胞定位 还将定义PBMC相关HBV DNA。 评估的水平 HBV DNA阳性单核细胞中病毒基因表达 细胞，将检查来自HTLV-III/LAV感染患者的PBMC的 RNA/DNA杂交法检测HBV特异性RNA及放射免疫分析 和蛋白质印迹技术检测病毒编码抗原的存在。 最后，将尝试建立体外模型， 共培养和转染方法，以确定HBV是否 淋巴细胞的感染可以影响复制或细胞病变， HTLV-III/LAV的潜力。 确定分子和生物学事件 PBMC内HBV增殖的影响将是至关重要的 阐明了HBV可能作为辅助因子在 HTLV-III引起的疾病。

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.