Enhancement of Zika virus pathogenesis by preexisting antiflavivirus immunity
Top Cited Papers
- 14 April 2017
- journal article
- other
- Published by American Association for the Advancement of Science (AAAS) in Science
- Vol. 356 (6334), 175-180
- https://doi.org/10.1126/science.aal4365
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.Keywords
Funding Information
- National Institute of Allergy and Infectious Diseases (award303923, R21AI130299)
- National Institute of Allergy and Infectious Diseases (award303924, U19AI118610)
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