Enhancement of Zika virus pathogenesis by preexisting antiflavivirus immunity

Susana V. Bardina, Paul Bunduc, Shashank Tripathi, James Duehr, Justin J. Frere, Julia A. Brown, Raffael Nachbagauer, Gregory A. Foster, David Krysztof, Domenico Tortorella, Susan L. Stramer, Adolfo García-Sastre, Florian Krammer, Jean K. Lim

Research output: Contribution to journalArticlepeer-review

416 Scopus citations

Abstract

Zika virus (ZIKV) is spreading rapidly into regions around the world where other flaviviruses, such as dengue virus (DENV) and West Nile virus (WNV), are endemic. Antibody-dependent enhancement has been implicated in more severe forms of flavivirus disease, but whether this also applies to ZIKV infection is unclear. Using convalescent plasma from DENV- and WNV-infected individuals, we found substantial enhancement of ZIKV infection in vitro that was mediated through immunoglobulin G engagement of Fcγ receptors. Administration of DENV- or WNV-convalescent plasma into ZIKV-susceptible mice resulted in increased morbidity - including fever, viremia, and viral loads in spinal cord and testes - and increased mortality. Antibody-dependent enhancement may explain the severe disease manifestations associated with recent ZIKV outbreaks and highlights the need to exert great caution when designing flavivirus vaccines.

Original languageEnglish
Pages (from-to)175-180
Number of pages6
JournalScience
Volume356
Issue number6334
DOIs
StatePublished - 14 Apr 2017

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