The male genital system as a temporary reservoir for the Zika virus: a systematic review

Dias, F. C. R.Silva, L. B.Oliveira, E. L.Carvalho, R. P. R.Gomes, M. L. M.

Abstract Arboviruses pose a significant global health threat, with millions of annual infections, resulting in thousands of deaths. The Zika virus (ZIKV) is particularly notorious, exhibiting sexual transmission due to its prolonged presence in sperm. This review aimed to understand viral spread, sites of viral replication in the male reproductive system, and the effects of infection on the testes, epididymis, accessory glands, and sperm. The systematic review was conducted following the PRISMA guidelines. The central research question posed was How does the virus impact the androgenic and gametogenic components, employing temporary reservoirs in murine models? The criteria for eligibility included studies focused on investigating the effects of Zika virus infection, comprehensive investigations evaluating organs within the male reproductive system, and studies conducted using murine models or in vitro experimental methodologies. Out of 1273 initially identified articles, 44 met the inclusion criteria for this review. ZIKV infection initiates in the epididymis through hematophagy or lymphogenous dissemination. As the infection progresses, a dynamic shift occurs, releasing pro-inflammatory factors that directly impact the stability of the Sertoli cell barrier, providing the virus with a safe place for replication and sustaining active viremia. Cells expressing high levels of AXL and Tyro3 are easily infected. Macrophages, Leydig cells, and Sertoli cells function as reservoirs for viral infection, while accessory glands serve as reservoirs for the virus released into the semen. This review underscores the importance of understanding the virus' behavior within the male reproductive organs.