HHV-8 VIRAL LOAD AND PROGRESSION TO KAPOSIS SARCOMA

HHV-8与卡波西氏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病毒已被证明感染B细胞，并存在于KS患者或KS高危人群的循环PBMC中。然而，这些人的PBMC中HHV-8DNA的存在是零星的。HHV-8出现在PBMC中与KS发病之间的关系尚不清楚，HHV-8血清转换后PBMC感染的确切时间和KS之前的发展也不清楚。我们的假设是，随着时间的推移，PBMC中的HHV-8病毒载量将预测进展为KS的可能性，个人的免疫状态(通过CD4计数来衡量)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的上升相关。这项建议中的研究目的是在研究过程中对血清转换为HHV-8的个人进行纵向研究，确定HHV-8在PBMC中的发生率和病毒载量。这项研究的PBMC来源将是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，该研究来自在MACS登记期间血清转换为HHV-8的MACS受试者(血清转换日期已知)。我们将比较那些患有KS的人和那些没有KS的人的结果。这些结果还将决定从HHV-8血清转换到KS发病期间外周血单核细胞中可检测到的HHV-8DNA水平的发生率。

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.