Cross-reactive Dengue virus-specific CD8+ T cells protect against Zika virus during pregnancy

Nat Commun. 2018 Aug 2;9(1):3042. doi: 10.1038/s41467-018-05458-0.


As Zika virus (ZIKV) emerges into Dengue virus (DENV)-endemic areas, cases of ZIKV infection in DENV-immune pregnant women may rise. Here we show that prior DENV immunity affects maternal and fetal ZIKV infection in pregnancy using sequential DENV and ZIKV infection models. Fetuses in ZIKV-infected DENV-immune dams were normal sized, whereas fetal demise occurred in non-immune dams. Moreover, reduced ZIKV RNA is present in the placenta and fetuses of ZIKV-infected DENV-immune dams. DENV cross-reactive CD8+ T cells expand in the maternal spleen and decidua of ZIKV-infected dams, their depletion increases ZIKV infection in the placenta and fetus, and results in fetal demise. The inducement of cross-reactive CD8+ T cells via peptide immunization or adoptive transfer results in decreased ZIKV infection in the placenta. Prior DENV immunity can protect against ZIKV infection during pregnancy in mice, and CD8+ T cells are sufficient for this cross-protection. This has implications for understanding the natural history of ZIKV in DENV-endemic areas and the development of optimal ZIKV vaccines.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD8-Positive T-Lymphocytes / immunology*
  • Cross Reactions / immunology*
  • Decidua / pathology
  • Dengue Virus / immunology*
  • Epitopes / immunology
  • Female
  • Fetus / pathology
  • Mice, Inbred C57BL
  • Phenotype
  • Pregnancy
  • Species Specificity
  • Spleen / immunology
  • Spleen / pathology
  • Viral Load
  • Zika Virus / immunology*
  • Zika Virus Infection / immunology
  • Zika Virus Infection / virology


  • Epitopes