Dengue virus sero-cross-reactivity drives antibody-dependent enhancement of infection with zika virus

Wanwisa Dejnirattisai, Piyada Supasa, Wiyada Wongwiwat, Alexander Rouvinski, Giovanna Barba-Spaeth, Thaneeya Duangchinda, Anavaj Sakuntabhai, Van Mai Cao-Lormeau, Prida Malasit, Felix A. Rey, Juthathip Mongkolsapaya, Gavin R. Screaton*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

679 Scopus citations


Zika virus (ZIKV) was discovered in 1947 and was thought to lead to relatively mild disease. The recent explosive outbreak of ZIKV in South America has led to widespread concern, with reports of neurological sequelae ranging from Guillain Barré syndrome to microcephaly. ZIKV infection has occurred in areas previously exposed to dengue virus (DENV), a flavivirus closely related to ZIKV. Here we investigated the serological cross-reaction between the two viruses. Plasma immune to DENV showed substantial cross-reaction to ZIKV and was able to drive antibody-dependent enhancement (ADE) of ZIKV infection. Using a panel of human monoclonal antibodies (mAbs) to DENV, we showed that most antibodies that reacted to DENV envelope protein also reacted to ZIKV. Antibodies to linear epitopes, including the immunodominant fusion-loop epitope, were able to bind ZIKV but were unable to neutralize the virus and instead promoted ADE. Our data indicate that immunity to DENV might drive greater ZIKV replication and have clear implications for disease pathogenesis and future vaccine programs for ZIKV and DENV.

Original languageAmerican English
Pages (from-to)1102-1108
Number of pages7
JournalNature Immunology
Issue number9
StatePublished - 19 Aug 2016
Externally publishedYes

Bibliographical note

Funding Information:
We thank Armed Forces Research Institute of Medical Sciences, Thailand for Vero cells, C6/36 cells, mAb 4G2 to DENV envelope protein, and viruses DENV- 1, DENV-2 and DENV-3; and M. Nguyen-De Bernon for technical assistance. Supported by the Medical Research Council, UK, the Wellcome Trust, UK (G.R.S.), the National Institute for Health Research Biomedical Research Centre, Funding Scheme, European Commission Seventh Framework Programme (FP7/2007- 2013) for the DENFREE project (under grant agreement 282 378), Laboratory of Excellence Integrative Biology of Emerging Infectious Diseases (ANR-10-LABX- 62-IBEID to F.A.R.), Agence Nationale de la Recherche (FlaviStem/I1378 to F.A.R.) and the Thailand Research Fund through the Royal Golden Jubilee PhD (P.S. and J.M.).

Publisher Copyright:
© 2016 Nature America, Inc.


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