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）的宿主细胞范围很大除了B细胞外，比最初相信的，现在还包括和上皮细胞，某些类型的T细胞。有人提出当同一个人是与HIV-1和EBV共同感染，EBV和HIV-1之间的协同作用被建议。以前我们已经证明了重叠的主机单元范围导致HIV-1表达改变和EBV诱导的转化在共同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菌株之间的协同作用在感染CD19+ B细胞均匀种群的过程中。许多与不受控制的EBV复制相关的病理方面是在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细胞降低的直接结果监视。不受控制的EBV对于与EBV相关的淋巴瘤至关重要发展。该提案的具体目的是使用已建立的在一种新方法中的技术来确定是否直接协同作用在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）和病毒营救以检测 EBV表达并测量CD3+，CD4+中的HIV-1负载。 CD8+，CD19+和来自正常EBV阳性个体的单核细胞/巨噬细胞，感染有和没有HIV-1阳性个体的患者淋巴瘤。淋巴瘤组将分为与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，他们选择了标准干预抗逆转录病毒疗法进行有或没有抗HERPES病毒疗法。两个都将纵向研究小组，并以（i）为特定目的确定淋巴瘤发育是否与病毒相关尤其是淋巴细胞亚群的负担，（ii）确定有或没有抗HERPES病毒的抗逆转录病毒疗法的作用淋巴细胞亚群中病毒负担的治疗。