Figure 1.

The dissemination process of ZIKV in male reproductive tract. In the male reproductive tract, Immune system mechanism might promote ZIKV dissemination. (1) ZIKV travel in infected immune cells such as Dendritic cells to testis; ZIKV NS1 protein increase the permeability of endothelial cells to allow virus access toward interstitial space, (2) ZIKV infect Leydig cells increase the production of viruses in the zone, (3) ZIKV can infect Sertoli cells and change the immunosuppressive microenvironment to a robust antiviral response. Activated macrophages secrete TNF-α that disrupt the Blood Testicular Barrier by degradation of tight junction proteins such as ZO-1 allowing ZIKV reach and infect germ cells, (4) In parallel, is possible that on infected Sertoli cells the NS2A protein target to degradation proteins of tight junction complexes helping also to reach germ cells, (5) Finally, through adhesion molecules such as VCAM-1 ZIKV infected macrophages can interact with Sertoli cells (6) and direct infiltrate the lumen of seminiferous tubules and ZIKV could infect eventually germinal cells.