SYNERGY BETWEEN EBV AND HIV 1 DURING LYMPHOGENESIS

EBV 和 HIV 1 在淋巴生成过程中的协同作用

• 批准号: 2108401
• 负责人: EARL E HENDERSON
• 金额: $ 27.79万
• 依托单位: TEMPLE UNIV OF THE COMMONWEALTH
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-08-01 至 1997-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2108401
• 关键词: AIDS therapy; B lymphocyte; CD antigens; Epstein Barr virus; antiviral agents; cell population study; cell sorting; gene expression; human immunodeficiency virus 1; human subject; human therapy evaluation; longitudinal human study; lymphocyte; lymphoma; macrophage; microorganism interaction; monocyte; neoplasm /cancer immunology; polymerase chain reaction; virus antigen; virus load

The host cell range for Epstein-Barr virus (EBV) is now known to be much broader than originally believed and now includes, in addition to B cells and epithelial cells, some types of T cells. It has been proposed that accelerated disease progression might occur when the same individual is coinfected with both HIV-1 and EBV and synergy between EBV and HIV-1 has been suggested. Previously we have shown that overlapping host cell range resulted in altered HIV-1 expression and EBV-induced transformation in coinfected peripheral blood lymphocytes (PBLs) and PBL subpopulations. We have also detected synergy between the IIIB strain of HIV-1 and EBV during infection of homogeneous population of CD19+ B cells. Many aspects of pathology associated with uncontrolled EBV replication are manifested during HIV-1 infection. Conventional thought is that the elevated levels of EBV expression are the direct result of reduced T cell surveillance. Uncontrolled EBV is essential for EBV-associated lymphomas to develop. The specific aim of this proposal is to use established techniques in a novel approach to determine whether direct synergy between EBV and HIV-1 occurs in vivo. Specifically, we will use quantitative polymerase chain reaction (PCR) and virus rescue to detect EBV expression and measure HIV-1 load in CD3+, CD4+. CD8+, CD19+ and monocytes/macrophages from normal EBV-seropositive individuals and patients infected with HIV-1-positive individuals with and without lymphoma. The lymphoma group will be subdivided into EBV-associated with non-EBV-associated. The second study group will consist of individuals newly diagnosed as HIV-1 who have chosen intervention with standard antiretroviral therapy with and without anti-herpes virus therapy. Both groups will be studied longitudinally, with the specific aims of (i) determining whether lymphoma development can be correlated with viral burden in particular lymphocyte subpopulations, and (ii) determining the effects of antiretroviral therapy with or without anti-herpes virus therapy on viral burden in lymphocyte subpopulations.

目前已知 Epstein-Barr 病毒 (EBV) 的宿主细胞范围非常广泛。 比最初认为的更广泛，现在除了 B 细胞之外还包括 和上皮细胞，某些类型的 T 细胞。 有人提议 当同一个人被 同时感染 HIV-1 和 EBV，并且 EBV 和 HIV-1 之间存在协同作用 被建议。 之前我们已经证明重叠的宿主细胞 范围导致 HIV-1 表达改变和 EBV 诱导的转化 共感染的外周血淋巴细胞 (PBL) 和 PBL 亚群。 我们还检测到 HIV-1 IIIB 毒株和 EBV 之间的协同作用 在感染同质 CD19+ B 细胞群时。 许多 与不受控制的 EBV 复制相关的病理学方面是 HIV-1感染期间表现出来。 传统的想法是， EBV 表达水平升高是 T 细胞减少的直接结果 监视。 不受控制的 EBV 对于 EBV 相关淋巴瘤至关重要 发展。 该提案的具体目标是利用既定的 一种新方法中的技术来确定是否存在直接协同作用 EBV 和 HIV-1 之间发生在体内。 具体来说，我们将使用 定量聚合酶链反应 (PCR) 和病毒救援检测 EBV 表达并测量 CD3+、CD4+ 中的 HIV-1 载量。 CD8+、CD19+ 和 来自正常 EBV 血清阳性个体的单核细胞/巨噬细胞和 感染或未感染 HIV-1 阳性个体的患者 淋巴瘤。 淋巴瘤组将细分为 EBV 相关性 非 EBV 相关。 第二个研究小组将由个人组成 新诊断为 HIV-1 并选择标准干预措施的人 联合或不联合抗疱疹病毒治疗的抗逆转录病毒治疗。 两个都 将纵向研究群体，具体目标是 (i) 确定淋巴瘤的发展是否与病毒相关 特定淋巴细胞亚群的负担，以及（ii）确定 联合或不联合抗疱疹病毒的抗逆转录病毒治疗的效果 对淋巴细胞亚群中病毒负荷的治疗。