Zika Virus Causes Testis Damage and Leads to Male Infertility in Mice

Cell. 2016 Dec 1;167(6):1511-1524.e10. doi: 10.1016/j.cell.2016.11.016. Epub 2016 Nov 21.

Abstract

Zika virus (ZIKV) persists in the semen of male patients, a first for flavivirus infection. Here, we demonstrate that ZIKV can induce inflammation in the testis and epididymidis, but not in the prostate or seminal vesicle, and can lead to damaged testes after 60 days post-infection in mice. ZIKV induces innate immune responses in Leydig, Sertoli, and epididymal epithelial cells, resulting in the production of pro-inflammatory cytokines/chemokines. However, ZIKV does not induce a rapid and abundant cytokine production in peritubular cell and spermatogonia, suggesting that these cells are vulnerable for ZIKV infection and could be the potential repositories for ZIKV. Our study demonstrates a correlation between ZIKV and testis infection/damage and suggests that ZIKV infection, under certain circumstances, can eventually lead to male infertility.

Keywords: AXL; Zika virus; male infertility; orchitis-epididymitis.

MeSH terms

  • Animals
  • Axl Receptor Tyrosine Kinase
  • Cytokines / metabolism
  • Epididymis / pathology
  • Epididymis / virology
  • Humans
  • Infertility, Male / pathology
  • Infertility, Male / virology*
  • Male
  • Mice
  • Proto-Oncogene Proteins / metabolism
  • Receptor Protein-Tyrosine Kinases / metabolism
  • Receptor, Interferon alpha-beta / genetics
  • Testis / pathology
  • Testis / virology*
  • Virus Internalization
  • Zika Virus / isolation & purification
  • Zika Virus / physiology*
  • Zika Virus Infection / pathology
  • Zika Virus Infection / transmission
  • Zika Virus Infection / virology*

Substances

  • Cytokines
  • Ifnar1 protein, mouse
  • Proto-Oncogene Proteins
  • Receptor, Interferon alpha-beta
  • Receptor Protein-Tyrosine Kinases
  • Axl Receptor Tyrosine Kinase