Chronic Disease Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.
Faculty of Medicine, Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario, Canada.
Am J Reprod Immunol. 2019 Jul;82(1):e13129. doi: 10.1111/aji.13129. Epub 2019 May 26.
Sperm are the major cells in semen. Human sperm possess a number of HIV-1 gp120 binding ligands including sulfogalactosylglycerolipid (SGG). However, the mechanisms of how sperm capture HIV-1 onto their surface are unclear. Furthermore, the ability of sperm to deliver HIV-1 to vaginal/cervical epithelial cells lining the lower female reproductive tract, as a first step in HIV-1 transmission, needs to be determined.
Sperm from healthy donors were incubated with dual-tropic HIV-1 (clinical isolate), and virus capture was determined by p24 antigen ELISA. The involvement of SGG in HIV-1 capture was assessed by determining K values of HIV-1 gp120-SGG binding as well as computational docking of SGG to the gp120 V3 loop. The ability of sperm-associated HIV-1 to infect peripheral blood mononuclear cells (PBMCs) and TZM-bl indicator cells was determined. Lastly, infection of vaginal (Vk2/E6E7), ectocervical (Ect1/E6E7), and endocervical (End1/E6E7) epithelial cells mediated by HIV-1-associated sperm was evaluated.
Sperm were able to capture HIV-1 in a dose-dependent manner, and the capture reached a maximum within 5 minutes. Captured HIV-1, however, could be removed from sperm by Percoll-gradient centrifugation. Affinity of gp120 for SGG was substantial, implicating sperm SGG in HIV-1 capture. Sperm-associated HIV-1 could productively infect PBMCs and TZM-bl cells, and was capable of being transmitted into vaginal/cervical epithelial cells.
Sperm are able to capture HIV-1, which remains infectious and is able to be transmitted into vaginal/cervical epithelial cells, a result indicating the importance of sperm in HIV transmission.
精子是精液中的主要细胞。人类精子具有许多 HIV-1 gp120 结合配体,包括硫酸半乳糖甘油酯(SGG)。然而,精子如何捕获 HIV-1 并将其表面的机制尚不清楚。此外,需要确定精子将 HIV-1 递送到阴道/宫颈上皮细胞的能力,这是 HIV-1 传播的第一步。
将来自健康供体的精子与双嗜性 HIV-1(临床分离株)孵育,并通过 p24 抗原 ELISA 测定病毒捕获。通过测定 HIV-1 gp120-SGG 结合的 K 值以及 SGG 与 gp120 V3 环的计算对接,评估 SGG 在 HIV-1 捕获中的作用。测定与精子相关的 HIV-1 感染外周血单核细胞(PBMC)和 TZM-bl 指示细胞的能力。最后,评估 HIV-1 相关精子介导的阴道(Vk2/E6E7)、宫颈外口(Ect1/E6E7)和宫颈内口(End1/E6E7)上皮细胞的感染。
精子能够以剂量依赖性方式捕获 HIV-1,并且在 5 分钟内达到最大捕获量。然而,通过 Percoll 梯度离心可以从精子中去除捕获的 HIV-1。gp120 与 SGG 的亲和力很高,这表明精子 SGG 参与了 HIV-1 的捕获。与精子相关的 HIV-1 能够有效地感染 PBMC 和 TZM-bl 细胞,并且能够传播到阴道/宫颈上皮细胞。
精子能够捕获 HIV-1,这种 HIV-1 仍然具有传染性,并且能够传播到阴道/宫颈上皮细胞,这一结果表明精子在 HIV 传播中的重要性。