Epididymal epithelium propels early sexual transmission of Zika virus in the absence of interferon signaling

Nat Commun. 2021 Apr 29;12(1):2469. doi: 10.1038/s41467-021-22729-5.


Recognition of Zika virus (ZIKV) sexual transmission (ST) among humans challenges our understanding of the maintenance of mosquito-borne viruses in nature. Here we dissected the relative contributions of the components of male reproductive system (MRS) during early male-to-female ZIKV transmission by utilizing mice with altered antiviral responses, in which ZIKV is provided an equal opportunity to be seeded in the MRS tissues. Using microRNA-targeted ZIKV clones engineered to abolish viral infectivity to different parts of the MRS or a library of ZIKV genomes with unique molecular identifiers, we pinpoint epithelial cells of the epididymis (rather than cells of the testis, vas deferens, prostate, or seminal vesicles) as a most likely source of the sexually transmitted ZIKV genomes during the early (most productive) phase of ZIKV shedding into the semen. Incorporation of this mechanistic knowledge into the development of a live-attenuated ZIKV vaccine restricts its ST potential.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • Cell Line
  • Chlorocebus aethiops
  • Epididymis / virology*
  • Epithelial Cells / virology*
  • Epithelium / virology
  • Female
  • Genitalia, Male / anatomy & histology
  • Genitalia, Male / virology
  • Male
  • Mice
  • Sexually Transmitted Diseases, Viral / transmission*
  • Vero Cells
  • Zika Virus
  • Zika Virus Infection / transmission*