Institut National de la Santé et de la Recherche Médicale, Unité 625, Institut Fédératif de Recherche 140, Rennes, France.
Am J Pathol. 2011 Nov;179(5):2397-408. doi: 10.1016/j.ajpath.2011.08.005. Epub 2011 Sep 15.
Semen represents the main vector of HIV dissemination worldwide, yet the origin of HIV in semen remains unclear. Viral populations distinct from those found in blood have been observed in semen, indicating local viral replication within the male genital tract. The seminal vesicles, the secretions of which constitute more than 60% of the seminal fluid, could represent a major source of virus in semen. This study is the first to investigate the susceptibility of human seminal vesicles to HIV infection both in vitro and in vivo. We developed and characterized an organotypic culture of human seminal vesicles to test for target cells and HIV infection, and, in parallel, analyzed the seminal vesicle tissues from HIV-infected donors. In vitro, in contrast to HIV-1 X4, HIV-1 R5 exposure induced productive infection. Infected cells consisted primarily of resident CD163(+) macrophages, often located close to the lumen. In vivo, HIV protein and RNA were also detected primarily in seminal vesicle macrophages in seven of nine HIV-infected donors, some of whom were receiving prolonged suppressive highly active antiretroviral therapy. These results demonstrate that human seminal vesicles support HIV infection in vitro and in vivo and, therefore, have the potential to contribute virus to semen. The presence of infected cells in the seminal vesicles of treated men with undetectable viremia suggests that this organ could constitute a reservoir for HIV.
精液是全球 HIV 传播的主要载体,但精液中 HIV 的起源仍不清楚。在精液中观察到与血液中不同的病毒群体,表明男性生殖道内存在局部病毒复制。精囊是精液的主要来源之一,其分泌物占精液的 60%以上。本研究首次在体外和体内研究了人类精囊对 HIV 感染的易感性。我们开发并表征了一种人精囊的器官型培养物,以检测靶细胞和 HIV 感染,并同时分析了 HIV 感染供体的精囊组织。在体外,与 HIV-1 X4 相反,HIV-1 R5 暴露诱导了有性繁殖的感染。感染细胞主要由常驻的 CD163(+)巨噬细胞组成,这些细胞通常位于管腔附近。在体内,在九名 HIV 感染供体中的七名中,也主要检测到 HIV 蛋白和 RNA 存在于精囊巨噬细胞中,其中一些供体正在接受长期抑制性高效抗逆转录病毒治疗。这些结果表明,人类精囊在体外和体内支持 HIV 感染,因此有潜力将病毒贡献到精液中。在病毒载量检测不到的接受治疗的男性的精囊中存在感染细胞,这表明该器官可能构成 HIV 的储存库。