In Vivo Replication Capacity Rather Than In Vitro Macrophage Tropism Predicts Efficiency of Vaginal Transmission of Simian Immunodeficiency Virus or Simian/Human Immunodeficiency Virus in Rhesus Macaques

We used the rhesus macaque model of heterosexual human immunodeficiency virus (HIV) transmission to test the hypothesis that in vitro measures of macrophage tropism predict the ability of a primate lentivirus to initiate a systemic infection after intravaginal inoculation. A single atraumatic intravaginal inoculation with a T-cell-tropic molecular clone of simian immunodeficiency virus (SIV), SIVmac239, or a dualtropic recombinant molecular clone of SIV, SIVmac239/1A11/239, or uncloned dualtropic SIVmac251 or uncloned dualtropic simian/human immunodeficiency virus (SHIV) 89.6-PD produced systemic infection in all rhesus macaques tested. However, vaginal inoculation with a dualtropic molecular clone of SIV, SIVmac1A11, resulted in transient viremia in one of two rhesus macaques. It has previously been shown that 12 intravaginal inoculations with SIVmac1A11 resulted in infection of one of five rhesus macaques (M. L. Marthas, C. J. Miller, S. Sutjipto, J. Higgins, J. Torten, B. L. Lohman, R. E. Unger, H. Kiyono, J. R. McGhee, P. A. Marx, and N. C. Pedersen, J. Med. Primatol. 21:99–107, 1992). In addition, SHIV HXBc2, which replicates in monkey macrophages, does not infect rhesus macaques following multiple vaginal inoculations, while T-cell-tropic SHIV 89.6 does (Y. Lu, P. B. Brosio, M. Lafaile, J. Li, R. G. Collman, J. Sodroski, and C. J. Miller, J. Virol. 70:3045–3050, 1996). These results demonstrate that in vitro measures of macrophage tropism do not predict if a SIV or SHIV will produce systemic infection after intravaginal inoculation of rhesus macaques. However, we did find that the level to which these viruses replicate in vivo after intravenous inoculation predicts the outcome of intravaginal inoculation with each virus.

我们以恒河猴（rhesus macaque）作为人类免疫缺陷病毒（HIV）异性传播的动物模型，验证"体外检测巨噬细胞嗜性（macrophage tropism）可预测灵长类慢病毒经阴道内接种（intravaginal inoculation）后引发全身感染的能力"这一假说。
单次无创伤阴道内接种嗜T细胞（T-cell-tropic）的猴免疫缺陷病毒（SIV）分子克隆SIVmac239、双重嗜性（dualtropic）SIV重组分子克隆SIVmac239/1A11/239、未克隆（uncloned）的双重嗜性SIVmac251，或未克隆的双重嗜性猴人免疫缺陷病毒（SHIV）89.6-PD，均可使所有受试恒河猴产生全身感染。
然而，经阴道接种双重嗜性SIV分子克隆SIVmac1A11后，仅2只受试恒河猴中的1只出现一过性病毒血症（transient viremia）。既往研究表明，经12次阴道内接种SIVmac1A11后，5只恒河猴中的1只被感染（M. L. Marthas、C. J. Miller、S. Sutjipto、J. Higgins、J. Torten、B. L. Lohman、R. E. Unger、H. Kiyono、J. R. McGhee、P. A. Marx及N. C. Pedersen，《医学灵长类学杂志》（J. Med. Primatol.），1992年，21卷：99–107页）。
此外，可在猴巨噬细胞中复制的SHIV HXBc2，经多次阴道内接种后无法感染恒河猴，而嗜T细胞的SHIV 89.6则可感染（Y. Lu、P. B. Brosio、M. Lafaile、J. Li、R. G. Collman、J. Sodroski及C. J. Miller，《病毒学杂志》（J. Virol.），1996年，70卷：3045–3050页）。
上述结果表明，体外检测巨噬细胞嗜性无法预测SIV或SHIV经阴道内接种恒河猴后是否会引发全身感染。但我们发现，这些病毒经静脉内接种（intravenous inoculation）后在体内的复制水平，可预测每种病毒经阴道内接种后的感染结局。