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

• Published in: Nature immunology Vol. 17; no. 9; pp. 1102 - 1108
• Main Authors: Dejnirattisai, Wanwisa, Supasa, Piyada, Wongwiwat, Wiyada, Rouvinski, Alexander, Barba-Spaeth, Giovanna, Duangchinda, Thaneeya, Sakuntabhai, Anavaj, Cao-Lormeau, Van-Mai, Malasit, Prida, Rey, Felix A, Mongkolsapaya, Juthathip, Screaton, Gavin R
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.09.2016; Nature Publishing Group
• Subjects: 631/250/1933; 631/250/255/2514; 631/326/596/1413; Adolescent; Antibodies, Monoclonal; Antibodies, Monoclonal - blood; Antibodies, Monoclonal - immunology; Antibodies, Neutralizing; Antibodies, Neutralizing - blood; Antibodies, Neutralizing - immunology; Antibodies, Viral; Antibodies, Viral - blood; Antibodies, Viral - immunology; Antibody-Dependent Enhancement; Bioinformatics; Biomedicine; Cells, Cultured; Child; Child, Preschool; Comorbidity; Computer Science; Cross Reactions; Dengue; Dengue - epidemiology; Dengue - immunology; Dengue fever; Dengue Virus; Dengue Virus - physiology; Development and progression; Epitope Mapping; Female; Flaviviridae; Flavivirus; Genetics; Guillain-Barre Syndrome; Guillain-Barre Syndrome - epidemiology; Human genetics; Humans; Immune response; Immunodominant Epitopes; Immunodominant Epitopes - immunology; Immunodominant Epitopes - metabolism; Immunology; Infectious Diseases; Life Sciences; Male; Medical research; Microbiology and Parasitology; Microcephaly; Microcephaly - epidemiology; Observations; Parasitology; Populations and Evolution; Protein Binding; Quantitative Methods; Santé publique et épidémiologie; South America; South America - epidemiology; Vector-borne diseases; Viral Envelope Proteins; Viral Envelope Proteins - immunology; Viral Envelope Proteins - metabolism; Virology; Virus Replication; Zika Virus; Zika Virus - physiology; Zika Virus Infection; Zika Virus Infection - epidemiology; Zika Virus Infection - immunology
• ISSN: 1529-2908; 1529-2916
• DOI: 10.1038/ni.3515

Infection with Zika virus has occurred in areas previously exposed to dengue virus, a closely related flavivirus. Screaton and colleagues find that monoclonal antibodies to dengue virus cross-react with Zika virus and enhance infection. 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.