Harouse J M, Tan R C, Gettie A, Dailey P, Marx P A, Luciw P A, Cheng-Mayer C
Aaron Diamond AIDS Research Center, The Rockefeller University, New York, New York, 10016, USA.
Virology. 1998 Aug 15;248(1):95-107. doi: 10.1006/viro.1998.9236.
Infection of macaques with chimeric simian/human immunodeficiency virus (SHIV) expressing the envelope protein of HIV-1 provides a model system for studying HIV-1 infection in humans. To this end, four rhesus macaques (Macaca mulatta) were given a single intravaginal (IVAG) inoculation of cell-free SHIVSF33A and longitudinal samples of peripheral blood and lymph nodes were analyzed for viremia, antigenemia, and various T-cell populations. Rhesus macaques infected IVAG with SHIVSF33A demonstrated a dramatic decrease in the CD4(+) PBMC subset in the initial weeks after viral exposure, a time that corresponded to peak in plasma viremia and antigenemia. Within 4 months of SHIVSF33A inoculation, partial to complete rebound of the CD4(+) PBMC was seen in these animals. Notably, the regeneration of the CD4(+) subset was associated with regeneration of the naive T-cell population and was concordant with clearance of plasma viremia. DNA heteroduplex tracking assays revealed transmission of minor variants within the SHIVSF33A inoculum to the IVAG-inoculated animals. The cell-free SHIVSF33A inoculum as well as virus isolated from animals early after transmission used the chemokine molecule CXCR4 as the primary cellular coreceptor, demonstrating that viruses expressing envelope glycoproteins of the syncytia inducing (SI) phenotype can be transported across the vaginal mucosa. Although none of the animals has yet to develop clinical symptoms of simian AIDS (SAIDS), infectious virus and viral nucleic acids could be persistently isolated from each animal. Furthermore, animals transfused with blood from IVAG-infected macaques drawn 2 weeks after inoculation suffered a more profound and sustained CD4(+) T-cell loss, persistent plasma viremia, and the development of SAIDS in one animal, indicating that IVAG-passaged SHIVSF33A was pathogenic. Taken together, these results establish that a pathogenic CXCR4-utilizing SHIVSF33A species crossed the cervicovaginal mucosa. Different courses of infection in the IVAG versus transfusion animals suggest that host-mediated responses elicited upon transmission across mucosal barriers may serve to limit viral replication and delay disease progression in the IVAG-infected animals.
用表达HIV-1包膜蛋白的嵌合猿猴/人类免疫缺陷病毒（SHIV）感染猕猴，为研究人类HIV-1感染提供了一个模型系统。为此，对4只恒河猴（猕猴）进行了单次阴道内（IVAG）接种无细胞SHIVSF33A，并对其外周血和淋巴结的纵向样本进行了病毒血症、抗原血症及各种T细胞群体分析。经IVAG感染SHIVSF33A的恒河猴在病毒暴露后的最初几周内，CD4(+) PBMC亚群显著减少，这一时期与血浆病毒血症和抗原血症的峰值相对应。在接种SHIVSF33A的4个月内，这些动物的CD4(+) PBMC出现部分至完全反弹。值得注意的是，CD4(+)亚群的再生与初始T细胞群体的再生相关，并且与血浆病毒血症的清除一致。DNA异源双链追踪分析显示，SHIVSF33A接种物中的次要变异体传播至IVAG接种的动物体内。无细胞SHIVSF33A接种物以及传播后早期从动物体内分离出的病毒均以趋化因子分子CXCR4作为主要细胞共受体，表明表达合胞体诱导（SI）表型包膜糖蛋白的病毒能够穿过阴道黏膜。尽管尚无动物出现猿猴艾滋病（SAIDS）的临床症状，但每只动物均可持续分离出感染性病毒和病毒核酸。此外，接种后2周接受来自IVAG感染猕猴血液输注的动物，其CD4(+) T细胞损失更为严重且持续时间更长，出现持续的血浆病毒血症，其中一只动物还发展为SAIDS，这表明经IVAG传代的SHIVSF33A具有致病性。综上所述，这些结果证实，一种利用CXCR4的致病性SHIVSF33A毒株穿过了宫颈阴道黏膜。IVAG感染动物与输血感染动物不同的感染过程表明，在病毒穿过黏膜屏障传播时引发的宿主介导反应可能有助于限制IVAG感染动物体内的病毒复制并延缓疾病进展。
