Zika virus (ZIKV) is an arbovirus that belongs to the family flaviviridae and is transmitted to man by Aedes mosquitos. It 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, a disorder in which the body’s immune system attacks part of the peripheral nervous system, to microcephaly. ZIKV infection has occurred in areas previously exposed to dengue virus (DENV), a flavivirus closely related to ZIKV.
The researchers 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, they 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. The 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.
This work is a collaborative effort among researchers from the BIOTEC Medical Biotechnology Research, the Imperial College London (UK), the Mahidol University (Thailand), the Institut Pasteur (France), and the Institut Louis Malardé (French Polynesia).
Ref: Dejnirattisai, W., Supasa, P., Wongwiwat, W., Rouvinski, A., Barba-Spaeth, G., Duangchinda, T., Sakuntabhai, A., Cao-Lormeau, V-M., Malasit, P., Rey, F.A., Mongkolsapaya, J. and Screaton, G.R (2016). Dengue virus sero-cross-reactivity drives antibody-dependent enhancement of infection with zika virus. Nature Immunology, 17, 1102–1108.