Dengue virus-reactive CD8+ T cells mediate cross-protection against subsequent Zika virus challenge

Nat Commun. 2017 Nov 13;8(1):1459. doi: 10.1038/s41467-017-01669-z.


Zika virus (ZIKV) and dengue virus (DENV) are antigenically related flaviviruses that share cross-reactivity in antibody and T cell responses, and co-circulate in increasing numbers of countries. Whether pre-existing DENV immunity can cross-protect or enhance ZIKV infection during sequential infection of the same host is unknown. Here, we show that DENV-immune Ifnar1 -/- or wild-type C57BL/6 mice infected with ZIKV have cross-reactive immunity to subsequent ZIKV infection and pathogenesis. Adoptive transfer and cell depletion studies demonstrate that DENV-immune CD8+ T cells predominantly mediate cross-protective responses to ZIKV. In contrast, passive transfer studies suggest that DENV-immune serum does not protect against ZIKV infection. Thus, CD8+ T cell immunity generated during primary DENV infection can confer protection against secondary ZIKV infection in mice. Further optimization of current DENV vaccines for T cell responses might confer cross-protection and prevent antibody-mediated enhancement of ZIKV infection.

Publication types

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

MeSH terms

  • Adoptive Transfer*
  • Animals
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / transplantation*
  • Cross Protection / immunology*
  • Dengue Virus / immunology*
  • Epitopes, T-Lymphocyte / immunology
  • Immune Sera / administration & dosage
  • Immune Sera / immunology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Receptor, Interferon alpha-beta / genetics
  • Zika Virus / immunology*
  • Zika Virus Infection / immunology
  • Zika Virus Infection / prevention & control*
  • Zika Virus Infection / virology


  • Epitopes, T-Lymphocyte
  • Ifnar1 protein, mouse
  • Immune Sera
  • Receptor, Interferon alpha-beta