Zika Virus in the Male Reproductive Tract

Abstract

Arthropod-borne viruses (arboviruses) are resurging across the globe. Zika virus (ZIKV) has caused significant concern in recent years because it can lead to congenital malformations in babies and Guillain-Barré syndrome in adults. Unlike other arboviruses, ZIKV can be sexually transmitted and may persist in the male reproductive tract. There is limited information regarding the impact of ZIKV on male reproductive health and fertility. Understanding the mechanisms that underlie persistent ZIKV infections in men is critical to developing effective vaccines and therapies. Mouse and macaque models have begun to unravel the pathogenesis of ZIKV infection in the male reproductive tract, with the testes and prostate gland implicated as potential reservoirs for persistent ZIKV infection. Here, we summarize current knowledge regarding the pathogenesis of ZIKV in the male reproductive tract, the development of animal models to study ZIKV infection at this site, and prospects for vaccines and therapeutics against persistent ZIKV infection.

Potent Restriction of Sexual Zika Virus Infection by the Lipid Fraction of Extracellular Vesicles in Semen

“…Long-term detection of ZIKV in semen and considerable damage to genital tissues in men ( Ma et al, 2016 ; Siemann et al, 2017 ) suggest that the male genital tract is a site of persistent replication of competent virus. This virus likely is present in ejaculated semen ( Govero et al, 2016 ; Ma et al, 2016 ; Joguet et al, 2017 ; Matusali et al, 2018 ; Robinson et al, 2018 ; Stassen et al, 2018 ), arguing against the defective virus explanation. In addition, primate and mouse studies both report successful transmission of ZIKV via semen ( Uraki et al, 2017 ; Gurung et al, 2020 ).…”

Zika virus infects human testicular tissue and germ cells

“…However, it might also reflect the ability of the virus to replicate in testicular cells in a noncytopathic manner. No or minimal cytopathic infection and persistence of ZIKV has been reported in different cell types, including human placental macrophages (37), brain microvascujci.org Volume 128 Number 10 October 2018 transmission of ZIKV from vasectomized men (63), and by ZIKV replication in human prostate cell lines and cell line-based organoids (64). Interestingly, we recently demonstrated in SIV-infected cynomolgus macaques that depending on the individuals, different male genital organs may be the source of the virus in semen (65).…”

The Cellular Impact of the ZIKA Virus on Male Reproductive Tract Immunology and Physiology

“…In a mouse model, ZIKV sexual transmission was recently characterized, showing that epididymal epithelial cells and leukocytes should be the main source of ZIKV RNA shedding [73]. ZIKV can persist and replicate in MRT [74]. In cases of ZIKV infection, is it known that SCs can support a high level of ZIKV replication [75,76].…”

“…Further studies in this area have explored the pathogenesis pathways and the host cellular response, suggesting potential targets to develop vaccines, including DNA-based vaccines. DNA-based vaccines, and live attenuated ZIKV have shown testicular protection against infection, avoiding atrophy, damage, and male infertility [74,115].…”