Rosenberg Y J, Lewis M G, Leon E C, Cafaro A, Eddy G A, Greenhouse J J
Henry M. Jackson Foundation Laboratories, Rockville, Maryland 20850.
AIDS Res Hum Retroviruses. 1994 Oct;10(10):1269-77. doi: 10.1089/aid.1994.10.1269.
The decline in CD4+ cells and increased viral DNA and RNA burden in the blood of human immunodeficiency virus (HIV)-infected individuals have been used as closely related correlates of disease progression. However, little is known about levels of total or unintegrated viral DNA in lymphoid tissue of HIV-infected patients and how they relate to CD4+ cell decline or disease progression. Exploiting the similarities between HIV- and simian immunodeficiency virus (SIV)-induced disease, we examined lymphoid organs and peripheral blood from SIV-infected macaques for total (pol) and unintegrated 2-LTR circular viral DNA by polymerase chain reaction (PCR). Two SIV isolates (SIVmac/251 and SIVmne/E11S) that differ markedly in their biological and clinical properties were studied. The results indicate that total viral DNA burdens vary considerably between isolates. There was no strong association between total viral DNA levels and CD4% in lymphoid tissues when isolates were compared and death was not associated with any particular level of viral pol DNA. In contrast, accumulation of unintegrated viral DNA was closely associated with decline in CD4/CD8 ratios in lymphoid organs and AIDS. The appearance of both pol and unintegrated viral DNA in thymus of infected macaques also emerged as one of the single best correlates or possible predictors of advanced disease yet studied. Their roles in pathogenesis are discussed.
人类免疫缺陷病毒（HIV）感染者血液中CD4+细胞数量的减少以及病毒DNA和RNA负荷的增加，已被用作疾病进展的密切相关指标。然而，对于HIV感染患者淋巴组织中总病毒DNA或未整合病毒DNA的水平，以及它们与CD4+细胞减少或疾病进展之间的关系，人们知之甚少。利用HIV和猴免疫缺陷病毒（SIV）所致疾病的相似性，我们通过聚合酶链反应（PCR）检测了SIV感染猕猴的淋巴器官和外周血中的总（pol）病毒DNA和未整合的2-LTR环状病毒DNA。我们研究了两种生物学和临床特性差异显著的SIV分离株（SIVmac/251和SIVmne/E11S）。结果表明，不同分离株之间的总病毒DNA负荷差异很大。比较分离株时，淋巴组织中的总病毒DNA水平与CD4%之间没有很强的相关性，死亡与任何特定水平的病毒pol DNA均无关联。相比之下，未整合病毒DNA的积累与淋巴器官中CD4/CD8比值的下降以及艾滋病密切相关。感染猕猴胸腺中pol病毒DNA和未整合病毒DNA的出现，也成为迄今所研究的晚期疾病的最佳单一相关指标或可能的预测指标之一。文中讨论了它们在发病机制中的作用。
