Human antibody responses after dengue virus infection are highly cross-reactive to Zika virus

L Priyamvada, KM Quicke… - Proceedings of the …, 2016 - National Acad Sciences
L Priyamvada, KM Quicke, WH Hudson, N Onlamoon, J Sewatanon, S Edupuganti…
Proceedings of the National Academy of Sciences, 2016National Acad Sciences
Zika virus (ZIKV) is an emerging mosquito-borne flavivirus of significant public health
concern. ZIKV shares a high degree of sequence and structural homology compared with
other flaviviruses, including dengue virus (DENV), resulting in immunological cross-
reactivity. Improving our current understanding of the extent and characteristics of this
immunological cross-reactivity is important, as ZIKV is presently circulating in areas that are
highly endemic for dengue. To assess the magnitude and functional quality of cross-reactive …
Zika virus (ZIKV) is an emerging mosquito-borne flavivirus of significant public health concern. ZIKV shares a high degree of sequence and structural homology compared with other flaviviruses, including dengue virus (DENV), resulting in immunological cross-reactivity. Improving our current understanding of the extent and characteristics of this immunological cross-reactivity is important, as ZIKV is presently circulating in areas that are highly endemic for dengue. To assess the magnitude and functional quality of cross-reactive immune responses between these closely related viruses, we tested acute and convalescent sera from nine Thai patients with PCR-confirmed DENV infection against ZIKV. All of the sera tested were cross-reactive with ZIKV, both in binding and in neutralization. To deconstruct the observed serum cross-reactivity in depth, we also characterized a panel of DENV-specific plasmablast-derived monoclonal antibodies (mAbs) for activity against ZIKV. Nearly half of the 47 DENV-reactive mAbs studied bound to both whole ZIKV virion and ZIKV lysate, of which a subset also neutralized ZIKV. In addition, both sera and mAbs from the dengue-infected patients enhanced ZIKV infection of Fc gamma receptor (FcγR)-bearing cells in vitro. Taken together, these findings suggest that preexisting immunity to DENV may impact protective immune responses against ZIKV. In addition, the extensive cross-reactivity may have implications for ZIKV virulence and disease severity in DENV-experienced populations.
National Acad Sciences