Increases in Endogenous or Exogenous Progestins Promote Virus-Target Cell Interactions within the Non-human Primate Female Reproductive Tract

Currently, there are mounting data suggesting that HIV-1 acquisition in women can be affected by the use of certain hormonal contraceptives. However, in non-human primate models, endogenous or exogenous progestin-dominant states are shown to increase acquisition. To gain mechanistic insights into this increased acquisition, we studied how mucosal barrier function and CD4+ T-cell and CD68+ macrophage density and localization changed in the presence of natural progestins or after injection with high-dose DMPA. The presence of natural or injected progestins increased virus penetration of the columnar epithelium and the infiltration of susceptible cells into a thinned squamous epithelium of the vaginal vault, increasing the likelihood of potential virus interactions with target cells. These data suggest that increasing either endogenous or exogenous progestin can alter female reproductive tract barrier properties and provide plausible mechanisms for increased HIV-1 acquisition risk in the presence of increased progestin levels.

目前，越来越多的研究证据表明，女性感染人类免疫缺陷病毒1型（HIV-1）的风险可受部分激素类避孕药物使用的影响。然而，在非人灵长类动物模型中，内源性或外源性孕激素占主导的生理状态已被证实会升高病毒感染风险。为深入解析该感染风险升高的潜在机制，我们探究了在天然孕激素存在或注射大剂量醋酸甲羟孕酮（DMPA）后，生殖道黏膜屏障功能、CD4阳性T细胞与CD68阳性巨噬细胞的密度及定位变化情况。研究结果显示，天然孕激素或注射用孕激素可增强病毒对柱状上皮的穿透能力，并促使易感细胞浸润至变薄的阴道穹窿鳞状上皮层中，进而提升病毒与靶细胞发生潜在相互作用的概率。上述数据表明，提升内源性或外源性孕激素水平均可改变女性生殖道的屏障特性，为孕激素水平升高时HIV-1感染风险上升提供了合理的机制解释。