Wei Q, Javadian A, Lausen N, Fultz P N
Department of Microbiology, University of Alabama at Birmingham, BBRB 511, Birmingham, Alabama 35294-2170, USA.
Virology. 2000 Oct 10;276(1):59-69. doi: 10.1006/viro.2000.0520.
Data are accumulating to show that the natural history of human immunodeficiency virus type 1 (HIV-1) in chimpanzees closely reproduces that in humans and is influenced by biologic properties of the infecting HIV-1 strain. To determine the distribution and relative amounts of HIV-1, proviral DNA in multiple tissues from a chimpanzee euthanized because of an abdominal tumor and kidney failure was quantified by nested PCR limiting-dilution assays. At death, 21 months after infection with HIV-1(JC499), this animal had a CD4(+) T-cell count of 268 and 1.7 x 10(5) copies of virion RNA/ml of plasma. The highest proviral burdens were in peripheral lymph nodes and blood, followed by lung, colon, and spleen; values ranged from 130 to 3350 proviral copies/microg DNA (equivalent to DNA in 150,000 cells). The lowest levels of virus were in the spinal cord, brain, and cecum (0.3 to 2.5 copies/microg DNA), with all other tissues harboring intermediate levels (6.8 to 114 copies/microg DNA). Viral burdens in all tissues were comparable to or greater than those reported for HIV-1-infected humans in all stages of disease. Immunohistochemistry for HIV-1 p24 Gag antigen revealed (i) trapping of HIV-1 on follicular dendritic cells in lymph node germinal centers and (ii) virus in the brain, where it was localized primarily to capillary endothelial cells in the cerebral cortex. Analysis of the genetic diversity of the Env V3 loop in tissues indicated that there was no apparent compartmentalization of HIV-1 variants. Of interest, in 83 of 94 (88.3%) clones sequenced, the unique GYGR motif at the tip of the V3 loop of HIV-1(JC499) had reverted to the more common GPGR. The results support the conclusion that HIV-1 has the potential to maintain high viral burdens in chimpanzees and to disseminate to most organs, including the central nervous system. The use of the chimpanzee model with HIV-1(JC499) (or related strains) in vaccine efficacy studies should prove valuable, especially when assessing protection against disease. Furthermore, comparison of both replicative properties of HIV-1(JC499) with SIVcpz strains and immune responses of chimpanzees infected with these viruses might provide new information about HIV pathogenesis.
越来越多的数据表明，1型人类免疫缺陷病毒（HIV-1）在黑猩猩体内的自然病程与在人类体内的情况极为相似，且受到感染的HIV-1毒株生物学特性的影响。为了确定HIV-1的分布及相对含量，我们通过巢式PCR极限稀释分析法对一只因腹部肿瘤和肾衰竭而实施安乐死的黑猩猩多个组织中的前病毒DNA进行了定量分析。在感染HIV-1（JC499）21个月后死亡时，这只动物的CD4（+）T细胞计数为268，血浆中病毒粒子RNA的拷贝数为1.7×10（5）/ml。前病毒载量最高的是外周淋巴结和血液，其次是肺、结肠和脾脏；数值范围为130至3350个前病毒拷贝/μg DNA（相当于150,000个细胞中的DNA）。病毒水平最低的是脊髓、脑和盲肠（0.3至2.5个拷贝/μg DNA），所有其他组织中的病毒水平处于中间范围（6.8至114个拷贝/μg DNA）。所有组织中的病毒载量与HIV-1感染人类疾病各阶段所报道的载量相当或更高。HIV-1 p24 Gag抗原的免疫组织化学分析显示：（i）HIV-1在淋巴结生发中心的滤泡树突状细胞上捕获；（ii）在脑中发现病毒，其主要定位于大脑皮质的毛细血管内皮细胞。对组织中Env V3环的遗传多样性分析表明，HIV-1变异体没有明显的区室化现象。有趣的是，在测序的94个克隆中有83个（88.3%），HIV-1（JC499）V3环顶端独特的GYGR基序已恢复为更常见的GPGR。这些结果支持了以下结论：HIV-1有能力在黑猩猩体内维持高病毒载量并传播至包括中枢神经系统在内的大多数器官。在疫苗效力研究中使用携带HIV-1（JC499）（或相关毒株）的黑猩猩模型应会被证明是有价值的，尤其是在评估对疾病的预防时。此外，将HIV-1（JC499）与SIVcpz毒株的复制特性以及感染这些病毒的黑猩猩的免疫反应进行比较，可能会提供有关HIV发病机制的新信息。
