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

• Authors: Lalita Priyamvada, Emory University; Kendra M. Quicke, Emory University; William Hudson, Emory University; Nattawat Onlamoon, Mahidol University; Jaturong Sewatanon, Emory University; Srilatha Edupuganti, Emory University; Kovit Pattanapanyasat, Mahidol University; Kulkanya Chokephaibulkit, Mahidol University; Mark Mulligan, Emory University; Patrick C. Wilson, University of Chicago; Rafi Ahmed, Emory University; Mehul Suthar, Emory University; Jens Wrammert, Emory University
• Journal Title: PNAS
• Volume: Volume 113, Number 28
• Publisher: Unites States National Academy of Sciences | 2016-07-12, Pages 7852-7857
• Type of Work: Article | Final Publisher PDF
• Publisher DOI: http://doi.org/10.1073/pnas.1607931113
• Subjects: Biology, Virology; Health Sciences, Epidemiology; Biology, Microbiology; Health Sciences, Immunology
• Keywords: Science & Technology; Multidisciplinary Sciences; Science & Technology - Other Topics; Zika virus; cross-reactivity; antibodies; B-cell responses; Fusion loop; Envelope protein; Neutralizing antibodies; Dependent enhancement; Disease severity; Glycoprotein; Micronesia; Epitopes; Burden; States

Abstract

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.