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

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‐1CS204 (clinical isolate), and virus capture was determined by p24 antigen ELISA. The involvement of SGG in HIV‐1 capture was assessed by determining Kd 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.

Vaginal Epithelium Transiently Harbours HIV-1 Facilitating Transmission

“…In this study, we examined interaction of HIV-1 with vaginal epithelium, widely regarded as the primary site for viral transmission, using Vk2/E6E7, an established cell line extensively used to model STIs/RTIs ( Pandit et al., 2019 ; Young et al., 2019 ; Brannon et al., 2020 ). Vk2/E6E7 exhibited an HIV-binding receptor phenotype (CD4-, CCR5-) similar to primary vaginal epithelial cells obtained from swab samples, as observed by flow cytometry.…”

Viral infection of sperm. Part 2. Human herpes viruses, human immunodeficiency virus, hepatitis C virus, Zika virus (review)

“…C. D. Young и соавт. [57] продемонстрировали передачу вируса в эпителиальные клетки влагалища и шейки матки после инкубации сперматозоидов с клиническим изолятом ВИЧ 1-го типа. Авторы продемонстрировали, что поверхностное связывание вируса опосредовано рядом лигандов, связывающих gp120 ВИЧ 1-го типа, и сделали заключение о роли сперматозоидов в качестве переносчика вируса при горизонтальном распространении инфекции (передаче половым партнерам).…”