Zika Virus Pathogenesis in Rhesus Macaques Is Unaffected by Pre-Existing Immunity to Dengue Virus

Nat Commun. 2017 Jun 23;8:15674. doi: 10.1038/ncomms15674.


Zika virus (ZIKV) is a re-emerging virus that has recently spread into dengue virus (DENV) endemic regions and cross-reactive antibodies (Abs) could potentially affect ZIKV pathogenesis. Using DENV-immune serum, it has been shown in vitro that antibody-dependent enhancement (ADE) of ZIKV infection can occur. Here we study the effects of pre-existing DENV immunity on ZIKV infection in vivo. We infect two cohorts of rhesus macaques with ZIKV; one cohort has been exposed to DENV 2.8 years earlier and a second control cohort is naïve to flaviviral infection. Our results, while confirming ADE in vitro, suggest that pre-existing DENV immunity does not result in more severe ZIKV disease. Rather our results show a reduction in the number of days of ZIKV viremia compared to naïve macaques and that the previous exposure to DENV may result in modulation of the immune response without resulting in enhancement of ZIKV pathogenesis.

Publication types

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

MeSH terms

  • Animals
  • Antibodies, Neutralizing / immunology
  • Antibodies, Viral / immunology
  • Antibody-Dependent Enhancement*
  • Cross Reactions / immunology
  • Cytokines / immunology
  • Dengue / immunology*
  • Dengue Virus
  • Humans
  • Immune Sera
  • K562 Cells
  • Macaca mulatta
  • Male
  • Models, Animal
  • Viral Envelope Proteins / immunology
  • Zika Virus / pathogenicity*
  • Zika Virus Infection / immunology*


  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Cytokines
  • Immune Sera
  • Viral Envelope Proteins