Human Antibody Responses After Dengue Virus Infection Are Highly Cross-reactive to Zika Virus
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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.
Kalimuddin S, Tham C, Chan Y, Hang S, Kunasegaran K, Chia A Nat Microbiol. 2025; 10(2):374-387.
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Hay J, Routledge I, Takahashi S Epidemics. 2024; 49:100806.
PMID: 39647462 PMC: 11649536. DOI: 10.1016/j.epidem.2024.100806.
Roth C, Pitard B, Levillayer L, Lay S, Vo H, Cantaert T PLoS Negl Trop Dis. 2024; 18(10):e0012601.
PMID: 39418312 PMC: 11521268. DOI: 10.1371/journal.pntd.0012601.
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Adam A, Wenzel R, Unger E, Reiche S, Jassoy C Viruses. 2024; 16(7).
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Morgenlander W, Chia W, Parra B, Monaco D, Ragan I, Pardo C Nat Commun. 2024; 15(1):5833.
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