The Wistar Institute, Philadelphia, PA, USA.
Caribbean Primate Research Center and Animal Resources Center, University of Puerto Rico (UPR), San Juan, United States.
Nat Commun. 2019 Aug 21;10(1):3753. doi: 10.1038/s41467-019-11814-5.
Semen is the vehicle for virion dissemination in the female reproductive tract (FRT) in male-to-female HIV transmission. Recent data suggests that higher frequency semen exposure is associated with activation of anti-HIV mechanisms in HIV negative sex workers. Here, we use a non-human primate (NHP) model to show that repeated vaginal exposure to semen significantly reduces subsequent infection by repeated low-dose vaginal SIVmac251 challenge. Repeated semen exposures result in lower CCR5 expression in circulating CD4+ T-cells, as well as higher expression of Mx1 (in correlation with IFNε expression) and FoxP3 in the cervicovaginal mucosa, and increased infiltration of CD4+ T-cells. Establishing in vivo evidence of competing effects of semen on transmission impacts our basic understanding of what factors may determine HIV infectivity in humans. Our results clearly indicate that repeated semen exposure can profoundly modulate the FRT microenvironment, paradoxically promoting host resistance against HIV acquisition.
精液是男性向女性 HIV 传播中病毒颗粒在女性生殖道（FRT）中传播的载体。最近的数据表明，更高频率的精液暴露与 HIV 阴性性工作者中抗 HIV 机制的激活有关。在这里，我们使用非人类灵长类动物（NHP）模型表明，反复阴道暴露于精液可显著降低随后通过重复低剂量阴道 SIVmac251 挑战感染的风险。反复的精液暴露导致循环 CD4+T 细胞中 CCR5 的表达降低，以及在宫颈阴道黏膜中 Mx1（与 IFNε表达相关）和 FoxP3 的表达增加，CD4+T 细胞的浸润增加。精液对传播的竞争影响的体内证据确立，影响了我们对哪些因素可能决定人类 HIV 感染性的基本理解。我们的研究结果清楚地表明，反复的精液暴露可以深刻地调节 FRT 微环境，矛盾地促进宿主对 HIV 感染的抵抗力。
