» Articles » PMID: 27354515

Human Antibody Responses After Dengue Virus Infection Are Highly Cross-reactive to Zika Virus

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.

Citing Articles

Vaccine-induced T cell responses control Orthoflavivirus challenge infection without neutralizing antibodies in humans.

Kalimuddin S, Tham C, Chan Y, Hang S, Kunasegaran K, Chia A Nat Microbiol. 2025; 10(2):374-387.

PMID: 39794472 PMC: 11790491. DOI: 10.1038/s41564-024-01903-7.


Serodynamics: A primer and synthetic review of methods for epidemiological inference using serological data.

Hay J, Routledge I, Takahashi S Epidemics. 2024; 49:100806.

PMID: 39647462 PMC: 11649536. DOI: 10.1016/j.epidem.2024.100806.


Zika virus T-cell based 704/DNA vaccine promotes protection from Zika virus infection in the absence of neutralizing antibodies.

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.


Serological Evidence of Zika Virus Infections in Sudan.

Adam A, Wenzel R, Unger E, Reiche S, Jassoy C Viruses. 2024; 16(7).

PMID: 39066208 PMC: 11281350. DOI: 10.3390/v16071045.


Precision arbovirus serology with a pan-arbovirus peptidome.

Morgenlander W, Chia W, Parra B, Monaco D, Ragan I, Pardo C Nat Commun. 2024; 15(1):5833.

PMID: 38992033 PMC: 11239951. DOI: 10.1038/s41467-024-49461-0.


References
1.
Cao-Lormeau V, Blake A, Mons S, Lastere S, Roche C, Vanhomwegen J . Guillain-Barré Syndrome outbreak associated with Zika virus infection in French Polynesia: a case-control study. Lancet. 2016; 387(10027):1531-1539. PMC: 5444521. DOI: 10.1016/S0140-6736(16)00562-6. View

2.
Priyamvada L, Cho A, Onlamoon N, Zheng N, Huang M, Kovalenkov Y . B Cell Responses during Secondary Dengue Virus Infection Are Dominated by Highly Cross-Reactive, Memory-Derived Plasmablasts. J Virol. 2016; 90(12):5574-85. PMC: 4886779. DOI: 10.1128/JVI.03203-15. View

3.
DICK G, KITCHEN S, HADDOW A . Zika virus. I. Isolations and serological specificity. Trans R Soc Trop Med Hyg. 1952; 46(5):509-20. DOI: 10.1016/0035-9203(52)90042-4. View

4.
Hsieh S, Tsai W, Wang W . The length of and nonhydrophobic residues in the transmembrane domain of dengue virus envelope protein are critical for its retention and assembly in the endoplasmic reticulum. J Virol. 2010; 84(9):4782-97. PMC: 2863728. DOI: 10.1128/JVI.01963-09. View

5.
Musso D, Gubler D . Zika Virus. Clin Microbiol Rev. 2016; 29(3):487-524. PMC: 4861986. DOI: 10.1128/CMR.00072-15. View