Infection of epididymal epithelial cells and leukocytes drives seminal shedding of Zika virus in a mouse model

摘要

Author summary While Zika virus (ZIKV) is primarily a mosquito-borne virus, there are now confirmed sexual transmission cases of ZIKV from infected males to their partners. Using a previously established mouse model of sexual transmission, ZIKV was herein demonstrated to infect the testes and epididymides concurrently, suggesting that testicular infection is not required to seed infection of the epididymides. Also, replication of ZIKV was visualized by staining for ZIKV negative-strand RNA. ZIKV replication in leukocytes, immature spermatids and epididymal epithelial cells correlated with the peak of sexual transmission potential. Spermatozoa were rarely observed to stain positive for ZIKV replicative RNA intermediates, demonstrating spermatozoa are likely not a major source of infectious virus in semen. In addition, a greater fraction of the infectious virus in seminal fluids was cell-free versus cell-associated, suggesting that cell-free virus is responsible for sexual transmission. Taken together, these data provide strong evidence for epididymal epithelial cells and leukocytes, and not spermatozoa, as the major sources of infectious ZIKV in semen.