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

• DOI: 10.1038/ni.3515
• Publication Date: 2016-06-24T16:47:27Z
• Authors: Wanwisa Dejniratt...; Piyada Supasa; Wiyada Wongwiwat; Alexander Rouvinski; Giovanna Barba-Sp...; Thaneeya Duangchinda; Anavaj Sakuntabhai; Van-Mai Cao-Lormeau; Prida Malasit; Felix A Rey; Juthathip Mongkol...; Gavin R Screaton
• Keywords: Male; OUTBREAK; MESH: Dengue; MESH: Dengue Virus; Virus Replication; Antibodies, Viral; MESH: Antibodies, Monoclonal; MESH: Antibodies, Neutralizing; MESH: Cross Reactions; Dengue; Viral Envelope Proteins; MESH: Child; Monoclonal; Viral; BRAIN; Child; Neutralizing; Cells, Cultured; [INFO.INFO-BI] Computer Science [cs]/Bioinformatics [q-bio.QM]; [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology; 0303 health sciences; Cultured; [SDV.BIBS] Life Sciences [q-bio]/Quantitative Methods [q-bio.QM]; Zika Virus Infection; Antibodies, Monoclonal; BRAZIL; [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM]; 3. Good health; 1107 Immunology; Child, Preschool; [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology; Microcephaly; Female; Life Sciences & Biomedicine; [SDV.MP.PAR] Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology; MESH: Cells, Cultured; Protein Binding; Adolescent; Cells; Immunology; 610; MESH: Immunodominant Epitopes; MESH: Zika Virus; [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics; Cross Reactions; Guillain-Barre Syndrome; Antibodies; MESH: Microcephaly; Article; NEUTRALIZING ANTIBODIES; 03 medical and health sciences; MESH: Zika Virus Infection; MESH: Protein Binding; Humans; [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology; Preschool; MESH: Adolescent; MESH: Antibody-Dependent Enhancement; MESH: Guillain-Barre Syndrome; MESH: Epitope Mapping; MESH: Humans; [SDV.GEN.GPO]Life Sciences [q-bio]/Genetics/Populations and Evolution [q-bio.PE]; Science & Technology; CHIKUNGUNYA VIRUS; Immunodominant Epitopes; MESH: Virus Replication; MESH: Child, Preschool; MESH: South America; Zika Virus; Dengue Virus; South America; Antibodies, Neutralizing; Antibody-Dependent Enhancement; MESH: Male; [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics; [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie; MESH: Viral Envelope Proteins; [SDV.GEN.GPO] Life Sciences [q-bio]/Genetics/Populations and Evolution [q-bio.PE]; [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie; [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM]; MESH: Female; MESH: Antibodies, Viral; Epitope Mapping

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.