HHV-8 VIRAL LOAD AND PROGRESSION TO KAPOSIS SARCOMA

HHV-8 病毒载量和进展为卡波西斯肉瘤

• 批准号: 6173985
• 负责人: FRANK J JENKINS
• 金额: $ 7.21万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-07-23 至 2001-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6173985
• 关键词: AIDS related neoplasm /cancer; CD4 molecule; HIV infections; Kaposi's sarcoma; clinical research; disease /disorder onset; disease /disorder proneness /risk; enzyme linked immunosorbent assay; human herpesvirus 8; human subject; immunofluorescence technique; longitudinal human study; lymphocyte; neoplastic growth; pathologic process; polymerase chain reaction; serology /serodiagnosis; virus DNA; virus load; virus related neoplasm /cancer

HHV-8 has been strongly linked to the development of Kaposi's sarcoma with viral DNA sequences found in all forms of the disease. The HHV-8 virus has been shown to infect B cells and to be present in circulating PBMCs of individuals with KS or at high risk for development of KS. The presence of HHV-8 DNA in PBMCs of these individuals however, is sporadic. The relationship between the appearance of HHV-8 in PBMCs and onset of KS is not well understood with the precise timing of a PBMC infection following HHV-8 seroconversion and preceding development of KS not known. Our hypothesis is that HHV-8 viral load within PBMCs will be predictive over time for progression to KS and that the immune status of the individual (measured by CD4 count) will control both the appearance and levels of HHV-8 in these cells. We also predict that the appearance of virus in PBMCs will correlate with rises in antibody titers against lytic and/or latent viral proteins. The goal of the research in this proposal is determine the occurrence rate and viral load of HHV-8 in PBMCs in a longitudinal study of individuals who have seroconverted to HHV-8 during the course of the study. The source of PBMCs for this research will be longitudinal PBMC specimens collected by the Multicenter AIDS Cohort Study (MACS). We will measure the occurrence rate and viral load of HHV-8 in a longitudinal study of PBMCs from MACS subjects who have seroconverted to HHV-8 during their enrollment in the MACS (and the date of seroconversion is known). We will compare results between those individuals who developed KS and those who remained KS-free. These results will also determine the rate of occurrence of detectable levels of HHV-8 DNA in the PBMCs from the time of HHV-8 seroconversion to the onset of KS.

HHV-8与卡波西肉瘤的发展密切相关，在所有形式的疾病中都发现了病毒DNA序列。HHV-8病毒已被证明可以感染B细胞，并存在于KS患者或KS高危人群的外周血中。然而，在这些个体的pbmc中存在HHV-8 DNA是零星的。HHV-8在PBMC中出现与KS发病之间的关系尚不清楚，HHV-8血清转化后PBMC感染的确切时间和之前KS的发展尚不清楚。我们的假设是，随着时间的推移，pbmc内的HHV-8病毒载量将预测进展为KS，并且个体的免疫状态（通过CD4计数测量）将控制这些细胞中HHV-8的外观和水平。我们还预测，pbmc中病毒的出现将与针对裂解和/或潜伏病毒蛋白的抗体滴度上升相关。本研究的目的是在研究过程中对血清转化为HHV-8的个体进行纵向研究，确定PBMCs中HHV-8的发生率和病毒载量。本研究的PBMC来源将是由多中心艾滋病队列研究（MACS）收集的纵向PBMC样本。我们将在一项纵向研究中测量HHV-8的发生率和病毒载量，这些研究对象来自MACS受试者，他们在MACS登记期间血清转化为HHV-8（血清转化日期已知）。我们将比较发生KS的人和没有发生KS的人的结果。这些结果还将确定从HHV-8血清转化到KS发病期间pbmc中可检测水平的HHV-8 DNA的发生率。