HHV-8 VIRAL LOAD AND PROGRESSION TO KAPOSIS SARCOMA

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病毒已被证明感染B细胞，并存在于患有KS或处于KS发展高风险的个体的循环PBMC中。 然而，HHV-8 DNA在这些个体的PBMC中的存在是零星的。 PBMC中HHV-8的出现与KS发作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KS的发生时间尚不清楚。我们的假设是PBMC内的HHV-8病毒载量将随着时间的推移预测KS的进展，并且个体的免疫状态（通过CD 4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，病毒在PBMC中的出现将与针对裂解和/或潜伏病毒蛋白的抗体滴度的升高相关。本提案中研究的目标是在研究过程中对血清转化为HHV-8的个体进行的纵向研究中确定PBMC中HHV-8的发生率和病毒载量。 本研究的PBMC来源为多中心AIDS队列研究（MACS）采集的纵向PBMC标本。 我们将在MACS受试者的PBMC纵向研究中测量HHV-8的发生率和病毒载量，这些受试者在入组MACS期间血清转化为HHV-8（血清转化日期已知）。 我们将比较那些发展KS的人和那些保持KS自由的人之间的结果。这些结果还将确定从HHV-8血清转化至KS发作期间PBMC中HHV-8 DNA可检测水平的发生率。

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.