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

Wanwisa Dejnirattisai (1) , Piyada Supasa (1, 2) , Wiyada Wongwiwat (1) , Alexander Rouvinski (3) , Giovanna Barba-Spaeth (3) , Thaneeya Duangchinda , Anavaj Sakuntabhai (4) , Van-Mai Cao-Lormeau (5) , Prida Malasit (2) , Félix A. Rey (3) , Juthathip Mongkolsapaya (1) , Gavin Screaton (1)

1 Imperial College London
2 Mahidol University [Bangkok]
3 Virologie Structurale - Structural Virology
4 Génétique fonctionnelle des Maladies infectieuses - Functional Genetics of Infectious Diseases
5 ILM - Institut Louis Malardé [Papeete]

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.

Domains: Computer Science [cs]; Bioinformatics [q-bio.QM]; Life Sciences [q-bio]; Quantitative Methods [q-bio.QM]; Life Sciences [q-bio]; Genetics; Human genetics; Life Sciences [q-bio]; Genetics; Populations and Evolution [q-bio.PE]; Life Sciences [q-bio]; Microbiology and Parasitology; Virology; Life Sciences [q-bio]; Microbiology and Parasitology; Parasitology; Life Sciences [q-bio]; Santé publique et épidémiologie

Wanwisa Dejnirattisai, Piyada Supasa, Wiyada Wongwiwat, Alexander Rouvinski, Giovanna Barba-Spaeth, et al.. Dengue virus sero-cross-reactivity drives antibody-dependent enhancement of infection with zika virus. Nature Immunology, 2016, 17 (9), pp.1102-1108. ⟨10.1038/ni.3515⟩. ⟨pasteur-02003950⟩