Impact of prior flavivirus immunity on Zika virus infection in rhesus macaques

Michael K. McCracken, Gregory D. Gromowski, Heather L. Friberg, Xiaoxu Lin, Peter Abbink, Rafael De La Barrera, Kenneth H. Eckles, Lindsey S. Garver, Michael Boyd, David Jetton, Dan H. Barouch, Matthew C. Wise, Bridget S. Lewis, Jeffrey R. Currier, Kayvon Modjarrad, Mark Milazzo, Michelle Liu, Anna B. Mullins, J. Robert Putnak, Nelson L. MichaelRichard G. Jarman*, Stephen J. Thomas

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

115 Scopus citations

Abstract

Studies have demonstrated cross-reactivity of anti-dengue virus (DENV) antibodies in human sera against Zika virus (ZIKV), promoting increased ZIKV infection in vitro. However, the correlation between in vitro and in vivo findings is not well characterized. Thus, we evaluated the impact of heterotypic flavivirus immunity on ZIKV titers in biofluids of rhesus macaques. Animals previously infected (≥420 days) with DENV2, DENV4, or yellow fever virus were compared to flavivirus-naïve animals following infection with a Brazilian ZIKV strain. Sera from DENV-immune macaques demonstrated cross-reactivity with ZIKV by antibody-binding and neutralization assays prior to ZIKV infection, and promoted increased ZIKV infection in cell culture assays. Despite these findings, no significant differences between flavivirus-naïve and immune animals were observed in viral titers, neutralizing antibody levels, or immune cell kinetics following ZIKV infection. These results indicate that prior infection with heterologous flaviviruses neither conferred protection nor increased observed ZIKV titers in this non-human primate ZIKV infection model.

Original languageEnglish
Article numbere1006487
JournalPLoS Pathogens
Volume13
Issue number8
DOIs
StatePublished - Aug 2017
Externally publishedYes

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