Testicular cell types and infection by Zika virus

The testicle surprisingly emerged as important for Zika virus (ZIKV) infection, viral persistence, and sexual transmission. Systemic infection traffics ZIKV to the cells of the testes via the hematogenous or lymphogenous routes. Studies in mice and humans have shown that Sertoli cells, spermatogonia, and primary spermatocytes are preferred targets of ZIKV infection, but Leydig cells in the interstitium are infected sparingly. ZIKV-infected testicular cells may harbor virus/viral RNA for months, suggesting viral persistence. ZIKV destroys infected testicular cells leading to atrophy, which is associated with low testosterone and inhibins levels, and may thus negatively impact fertility in men. Testicular atrophy appears to be a slow process because ZIKV infection of the testis does not cause a dramatic induction of genes that cause apoptotic cell death. Nevertheless, ZIKV infection of the testis is important for persistence and sexual transmission. The ZIKV-host cell relationship is intriguingly complex and requires further study.