Zika virus (ZIKV) is a teratogenic mosquito-borne flavivirus which can be sexually transmitted from man to woman. High viral loads and prolonged viral shedding in semen suggest that ZIKV replicates within the human male genital tract, but its target organs are unknown. Using ex vivo infection of organotypic cultures, we demonstrated here that ZIKV replicates in human testicular tissue and infects a broad range of cell types, including germ cells, which we also identified as infected in the semen from ZIKV-infected donors. ZIKV had no major deleterious effect on the morphology and hormonal production of the human testis explants. Infection induced a broad antiviral response but no interferon up-regulation and minimal pro-inflammatory response in testis explants, with no cytopathic effect. Finally, we studied ZIKV infection in mouse testis, and compared it to human infection. This study provides key insights into how ZIKV may persist in semen and alter semen parameters, as well as a valuable tool for testing antiviral agents.
Giulia Matusali, Laurent Houzet, Anne-Pascale Satie, Dominique Mahé, Florence Aubry, Thérèse Couderc, Julie Frouard, Salomé Bourgeau, Karim Bensalah, Sylvain Lavoué, Guillaume Joguet, Louis Bujan, André Cabié, Gleide F. Avelar, Marc Lecuit, Anna Le Tortorec, Nathalie Dejucq-Rainsford