VIRAL COFACTORS IN HIV INFECTION AS TARGETS FOR THERAPY

我们建议通过以下方法确定抗病毒治疗的特异性靶点： 研究人类致病的病毒决定因素 免疫缺陷病毒（HIV）。 有丰富的分子， 病毒学和流行病学证据表明，病毒辅因子， 特别是EB病毒（EBV）和巨细胞病毒（CMV）， 可能参与艾滋病相关综合征的发病 (ARC)和艾滋病 因此，我们计划研究 感染HIV的细胞。 抗病毒治疗可以 针对的是被确定为可能的辅因子的病毒， 艾滋病毒感染的发展以及艾滋病毒本身。 我们计划进行原位杂交和免疫组织化学 用于分析HIV感染者的组织和细胞的染色 血清反应阳性的，有ARC的，有艾滋病的，还有对照组。 我们 目的是确定表达HIV的细胞是否也 显示EBV或CMV表达或接近这些细胞。 大量的淋巴组织，骨髓，大脑， 外周血淋巴细胞将使用原位 杂交法检测HIV RNA及免疫组化 染色以检测EBV和CMV抗原;此外， 使用原位杂交检测CMV RNA， 免疫组化检测HIV抗原表达。 我们 还将检查细胞的空间关系， 这些病毒的表达。 在人体组织中 在没有机会性感染的情况下， 相同的细胞或与表达HIV的细胞相邻的细胞会加入 已经存在的体外证据表明， 病毒可能在HIV感染的进展中起辅助因子的作用。 此外，我们还将进行一系列实验， CMV或EBV是否可以增强HIV的产生， 体外;如果证明体外增强，我们将进行测试， 如果这种作用可以被抑制CMV或EBV的药物阻断， 复制的

We proposed to identify specific targets for antiviral therapy by investigating the viral determinants of pathogenesis by the human immunodeficiency virus (HIV). There is abundant molecular, virologic, and epidemiologic evidence that viral cofactors, particularly Epstein-Barr virus (EBV) and cytomegalovirus (CMV), may be involved in the pathogenesis of AIDS related complex (ARC) and AIDS. We therefore plan to examine the relationship of these viruses to HIV infected cells. Antiviral therapy may then be aimed at the virus identified as a probable cofactor in the progression of HIV infection as well as at HIV itself. We plan to perform in situ hybridization and immunohistochemical staining to analyze tissues and cells from individuals who are HIV seropositive and well, have ARC, have AIDS, and controls. We aim to determine if cells demonstrating expression of HIV also show expression of EBV or CMV or border on such cells. Numerous samples of lymphoid tissue, bone marrow, brain, and peripheral blood lymphocytes will be examined using in situ hybridization to detect HIV RNA and immunohistochemical staining to detect EBV and CMV antigen; in addition tissues will be examined using in situ hybridization to detect CMV RNA and immunohistochemistry to detect expression of HIV antigen. We shall also examine the spatial relationship of cells showing expression of these viruses. In tissues derived from people without opportunistic infections, expression of CMV or EBV in the same cells or cells neighboring those expressing HIV will add in vivo evidence to the already existing in vitro evidence that these viruses may act as cofactors in the progression of HIV infection. In addition, we shall perform a series of experiments to assay whether CMV or EBV can potentiate the production of HIV in vitro; if in vitro potentiation is demonstrated, we shall test to see if this effect can be blocked by agents that inhibit CMV or EBV replication.