Significance In this study, we address the issue of cross-reactivity between dengue virus (DENV) and Zika virus (ZIKV) by testing sera and plasmablast-derived monoclonal antibodies from dengue patients against ZIKV. We show that both acute and convalescent dengue sera potently bind and neutralize ZIKV and that this cross-reactivity is also evident at the monoclonal level. We also demonstrate in vitro antibody-dependent enhancement of ZIKV infection in the presence of dengue-induced antibodies. Our findings strongly suggest that preexisting dengue antibodies may modulate immune responses to ZIKV infection. These data are timely and highly relevant from a public health standpoint given that a majority of regions currently experiencing Zika virus epidemics are endemic for dengue.
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