VIRAL COFACTORS IN HIV INFECTION AS TARGETS FOR THERAPY

我们建议通过以下方式确定抗病毒治疗的特定靶点 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， 尤其是EB病毒(EBV)和巨细胞病毒(CMV)， 可能参与艾滋病相关复合体的发病机制 (ARC)和艾滋病。因此，我们计划审查这一关系 将这些病毒转移到感染艾滋病毒的细胞。到那时，抗病毒治疗可能 针对被确认为可能是 艾滋病毒感染的进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 对HIV感染者的组织和细胞进行染色分析 血清阳性，有ARC，有艾滋病，有控制性疾病。我们 目的确定表现出HIV表达的细胞是否也 显示EBV或CMV的表达或边界。 大量的淋巴组织，骨髓，脑和 外周血淋巴细胞将进行原位检测 杂交法检测HIV-RNA和免疫组织化学 染色以检测EBV和CMV抗原；此外，组织将 用原位杂交检测CMV RNA和 免疫组织化学方法检测HIV抗原的表达。我们 还应检查显示的单元格的空间关系 这些病毒的表达。从人类提取的组织中 在没有机会性感染的情况下，CMV或EBV在 同样的细胞或表达艾滋病毒的细胞邻近的细胞将加入 已经存在的体外证据的活体证据表明 病毒可能在艾滋病毒感染的发展过程中起辅助因素的作用。 此外，我们还将进行一系列实验来分析 无论是CMV还是EBV都能增强人类免疫缺陷病毒的产生 体外；如果体外增强作用得到证实，我们将进行测试，以了解 如果这种作用可以被抑制CMV或EBV的药物所阻断 复制。

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.