**7. Conclusions**

ZIKV can infect and persist in testicular somatic and germ cells, as well as, spermatozoa, leading to cell death and testicular atrophy. ZIKV has also been detected in semen samples from ZIKV-infected patients. This has huge implications for human reproduction. DNA-based vaccination and/or live attenuated ZIKV vaccines showed high e fficacy against MRT damage induced by ZIKV and are a very prominent therapeutic tool to prevent male infertility caused by ZIKV.

It is important to note that, often, no evident testicular inflammatory response is usually observed against ZIKV infection in testes, with normal testicular morphology and hormone production remaining una ffected after ZIKV infection. This indicates that ZIKV can remain quiescent in the testes, acting as a trojan horse, and maintaining asymptomatic ZIKV sexual transmission. The better understanding of the mechanisms that mediate the cellular impact of the ZIKV on MRT, regulating testicular immune and physiological responses, is the key factor to the correct design of e fficient anti-ZIKV therapeutic strategies to prevent male infertility caused by ZIKV.

**Author Contributions:** R.d.N.A., H.A.B.-d.-M., I.d.O.S., R.C. and K.G.M. wrote the manuscript. R.d.N.A., I.d.O.S. and H.A.B.-d.-M. generated original figures. G.P.K. edited the manuscript. All authors have read and agreed to the published version of the manuscript.

**Funding:** The authors declare no funding for this manuscript.

**Conflicts of Interest:** The authors declare no conflict of interest.
