Zika virus infection damages the testes in mice

Abstract

Infection of male mice with Zika virus caused testicular and epididymal damage, reduction in sex hormone levels, destruction of germ and somatic cells in the testis, loss of mature sperm and reduction in fertility. Using a mouse-adapted strain of Zika virus, Michael Diamond and colleagues show that Zika virus infection of mice causes injury to the testes, resulting in diminished testosterone and oligospermia. They show that the virus preferentially infects spermatogonia, spermatocytes and Sertoli cells in the testis and causes the destruction of the seminiferous tubules. Longitudinal studies of sperm function and viability in of Zika virus infected humans are needed before the extent to which these observations translate to humans is clear. Infection of pregnant women with Zika virus (ZIKV) can cause congenital malformations including microcephaly, which has focused global attention on this emerging pathogen1. In addition to transmission by mosquitoes, ZIKV can be detected in the seminal fluid of affected males for extended periods of time and transmitted sexually2. Here, using a mouse-adapted African ZIKV strain (Dakar 41519), we evaluated the consequences of infection in the male reproductive tract of mice. We observed persistence of ZIKV, but not the closely related dengue virus (DENV), in the testis and epididymis of male mice, and this was associated with tissue injury that caused diminished testosterone and inhibin B levels and oligospermia. ZIKV preferentially infected spermatogonia, primary spermatocytes and Sertoli cells in the testis, resulting in cell death and destruction of the seminiferous tubules. Less damage was caused by a contemporary Asian ZIKV strain (H/PF/2013), in part because this virus replicates less efficiently in mice. The extent to which these observations in mice translate to humans remains unclear, but longitudinal studies of sperm function and viability in ZIKV-infected humans seem warranted.