Abstract
Sexual Zika virus (ZIKV) transmission from men to women occurs less frequently than the often-detected high viral loads in semen would suggest, but worries that this transmission route predisposes to fetal damage in pregnant women remain. To better understand sexual ZIKV pathogenesis, we studied the permissiveness of the human female genital tract to infection and the effect of semen on this process. ZIKV replicates in vaginal tissues and primary epithelial cells from the vagina, ectocervix, and endocervix and induces an innate immune response, but also continues to replicate without cytopathic effect. Infection of genital cells and tissues is strongly inhibited by extracellular vesicles (EV) in semen at physiological vesicle-to-virus ratios. Liposomes with the same composition as semen EVs also impair infection, indicating that the EV’s lipid fraction, rather than their protein or RNA cargo, is responsible for this anti-viral effect. Thus, EVs in semen potently restrict ZIKV transmission, but the virus propagates well once infection in the recipient mucosa has been established.
Highlights
Since the emergence of Zika virus (ZIKV) in the Americas, millions of people have been infected and transmission of virus continues in many areas (Siedner et al, 2018)
Oncogene-untransformed, epithelial cell lines from vaginal, ectocervical, and endocervical human tissues (Hladik et al, 2007, 2015). These cells were infected with Zika VR-1848, a strain isolated from the placenta of a patient in Honduras, at a multiplicity of infection (MOI) of 1
Our findings show that ZIKV productively infects primary epithelial cells of the female genital tract, inducing an antiviral immune response, yet continues to replicate without cytotoxic effect
Summary
Since the emergence of Zika virus (ZIKV) in the Americas, millions of people have been infected and transmission of virus continues in many areas (Siedner et al, 2018). The risk to fetuses of greater infection rates, higher viral loads, and morbidity and mortality, is increased following vaginal, compared to subcutaneous or intraperitoneal exposure to ZIKV (Yockey et al, 2016; Winkler et al, 2017; Duggal et al, 2018). These findings suggest that the pathogenesis of ZIKV varies by the route of transmission and highlight the need to thoroughly understand sexually transmitted ZIKV infections. Semen, which is co-delivered to the vaginal tract at the same time as virus, was absent from these studies, and it is important to understand how factors in semen influence ZIKV infection
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