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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

基本信息

批准号：
2108402
负责人：
EARL E HENDERSON
金额：
$ 29.24万
依托单位：
TEMPLE UNIV OF THE COMMONWEALTH
依托单位国家：
美国
项目类别：
财政年份：
1994
资助国家：
美国
起止时间：
1994-08-01 至 1998-07-31
项目状态：
已结题

项目摘要

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.

现在已知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细胞外，以及上皮细胞和某些类型的T细胞。已经提出当同一个人同时患有 HIV-1和EBV同时感染，EBV和HIV-1之间的协同作用被建议。以前我们已经表明，重叠的宿主细胞范围导致改变的HIV-1表达和EBV诱导的转化在共感染的外周血淋巴细胞（PBL）和PBL亚群中。我们还检测到HIV-1和EBV的IIIB株之间的协同作用在CD 19 + B细胞的同质群体的感染期间。许多与不受控制的EBV复制相关的病理学方面是在HIV-1感染期间出现。传统观点认为， EBV表达水平升高是T细胞减少的直接结果，监视未控制的EBV是EBV相关淋巴瘤的关键发展。该提案的具体目的是利用现有的技术在一种新的方法，以确定是否直接协同 EB病毒和HIV-1之间的相互作用是在体内发生的。具体来说，我们将使用定量聚合酶链反应（PCR）和病毒拯救检测检测CD 3+、CD 4+细胞中EBV的表达及HIV-1的载量。CD 8+、CD 19+和来自正常EBV血清阳性个体的单核细胞/巨噬细胞，感染HIV-1阳性个体的患者，淋巴瘤淋巴瘤组将被细分为EBV相关的非EBV相关。第二个研究小组将由个人组成，新诊断为HIV-1的人选择了标准的干预措施，抗逆转录病毒治疗与抗疱疹病毒治疗。两将对各群体进行纵向研究，具体目标如下：确定淋巴瘤的发展是否与病毒相关特别是淋巴细胞亚群的负荷，和（ii）确定抗逆转录病毒治疗与抗或不抗疱疹病毒治疗的效果淋巴细胞亚群中病毒负荷的治疗。