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精子可以作为 HIV-1 传播到阴道和宫颈上皮细胞的载体。

Sperm can act as vectors for HIV-1 transmission into vaginal and cervical epithelial cells.

机构信息

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.

出版信息

Am J Reprod Immunol. 2019 Jul;82(1):e13129. doi: 10.1111/aji.13129. Epub 2019 May 26.

Abstract

PROBLEM

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.

METHOD OF STUDY

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.

RESULTS

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.

CONCLUSION

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.

摘要

问题

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。

研究方法

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。

结果

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。

结论

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。

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