The possible role of cross-reactive dengue virus antibodies in Zika virus pathogenesis

PLoS Pathog. 2019 Apr 18;15(4):e1007640. doi: 10.1371/journal.ppat.1007640. eCollection 2019 Apr.


Zika virus (ZIKV) has been known for decades to circulate in Africa and Asia. However, major complications of a ZIKV infection have recently become apparent for reasons that are still not fully elucidated. One of the hypotheses for the seemingly increased pathogenicity of ZIKV is that cross-reactive dengue antibodies can enhance a ZIKV infection through the principle of antibody-dependent enhancement (ADE). Recently, ADE in ZIKV infection has been studied, but conclusive evidence for the clinical importance of this principle in a ZIKV infection is lacking. Conversely, the widespread circulation of ZIKV in dengue virus (DENV)-endemic regions raises new questions about the potential contribution of ZIKV antibodies to DENV ADE. In this review, we summarize the results of the evidence to date and elaborate on other possible detrimental effects of cross-reactive flavivirus antibodies, both for ZIKV infection and the risk of ZIKV-related congenital anomalies, DENV infection, and dengue hemorrhagic fever.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antibodies, Viral / immunology*
  • Antibody-Dependent Enhancement / immunology*
  • Cross Reactions / immunology*
  • Cytopathogenic Effect, Viral / immunology*
  • Dengue / immunology*
  • Dengue / virology
  • Humans
  • Zika Virus / pathogenicity*
  • Zika Virus Infection / immunology*
  • Zika Virus Infection / prevention & control
  • Zika Virus Infection / virology


  • Antibodies, Viral

Grants and funding

This project has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement ZikAlliance No 734548 and from the ZikaRisk project of ZonMw under project number 522003001. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.