Humoral cross-reactivity between Zika and dengue viruses: implications for protection and pathology

Abstract

Zika virus (ZIKV) is a re-emerging mosquito-borne flavivirus that has recently caused extensive outbreaks in Central and South America and the Caribbean. Given its association with Guillain–Barré syndrome in adults and neurological and ocular malformities in neonates, ZIKV has become a pathogen of significant public health concern worldwide. ZIKV shares a considerable degree of genetic identity and structural homology with other flaviviruses, including dengue virus (DENV). In particular, the surface glycoprotein envelope (E), which is involved in viral fusion and entry and is therefore a chief target for neutralizing antibody responses, contains regions that are highly conserved between the two viruses. This results in immunological cross-reactivity, which in the context of prior DENV exposure, may have significant implications for the generation of immune responses to ZIKV and affect disease outcomes. Here we address the issue of humoral cross-reactivity between DENV and ZIKV, reviewing the evidence for and discussing the potential impact of this cross-recognition on the functional quality of antibody responses against ZIKV. These considerations are both timely and relevant to future vaccine design efforts, in view of the existing overlap in the distribution of ZIKV and DENV and the likely spread of ZIKV to additional DENV-naive and experienced populations.

Emerging Microbes & Infections (2017) 6, e33; doi:10.1038/emi.2017.42; published online 10 May 2017

• antibody-dependent enhancement
• cross-protection
• cross-reactive antibodies
• DENV
• ZIKV

Acknowledgments

This work was funded in part by NIH/NIAID Grant U19AI057266 and 1U01AI115651 to RA and JW. WH is a Cancer Research Institute Irvington Fellow supported by the Cancer Research Institute. All three authors are affiliated with Emory University School of Medicine, Atlanta, GA 30322, USA.