UNRAVELING THE STRUCTURAL AND IMMUNOLOGICAL MECHANISMS OF CROSS-REACTIVITY IN DENGUE VIRUS AND ZIKA VIRUS CO-INFECTION

S YOUNAS; U ZAHOOR; S MANZOOR; MZ SALEEM; Q ALI

doi:10.64013/bbasr.v2026i1.129

Authors

S YOUNAS Centre for Applied Molecular Biology, University of the Punjab, Lahore, Pakistan
U ZAHOOR Centre for Applied Molecular Biology, University of the Punjab, Lahore, Pakistan
S MANZOOR Centre for Applied Molecular Biology, University of the Punjab, Lahore, Pakistan
MZ SALEEM Centre for Applied Molecular Biology, University of the Punjab, Lahore, Pakistan
Q ALI Department of Plant Breeding and Genetics, Faculty of Agricultural Sciences, University of the Punjab, P.O BOX. 54590, Lahore, Pakistan

DOI:

https://doi.org/10.64013/bbasr.v2026i1.129

Keywords:

DENV, ZIKV, cross-reactivity, antibodies, Co-infection

Abstract

Dengue virus (DENV) co-infection with Zika virus (ZIKV) presents a significant health challenge, primarily due to their shared transmission by Aedes aegypti mosquitoes. In recent years, Zika outbreaks have occurred in areas where dengue is endemic. The widespread presence of mosquito vectors facilitates simultaneous infection with both viruses at the same time in these areas. Both DENV and ZIKV are flaviviruses, and there are significant clinical and structural similarities. Because of this structural similarity, there can be cross-reactivity, and this cross-reactive immune response may result in false-positive serological results, especially for those who have a secondary infection. This cross-reactivity can therefore lead to an overestimation of the prevalence of Zika in areas where dengue is common. This review explores the structural similarities between DENV and ZIKV and the mechanisms of immunological cross-reactivity at both structural and cellular levels. It discusses the challenges associated with accurately assessing the prevalence of dengue and Zika co-infections.

Downloads

Download data is not yet available.

References

Aisenberg, L. K., Rousseau, K. E., Cascino, K., Massaccesi, G., Aisenberg, W. H., Luo, W., Muthumani, K., Weiner, D. B., Whitehead, S. S., and Chattergoon, M. A. (2022). Cross-reactive antibodies facilitate innate sensing of dengue and Zika viruses. JCI insight 7.

Balmaseda, A., Stettler, K., Medialdea-Carrera, R., Collado, D., Jin, X., Zambrana, J. V., Jaconi, S., Cameroni, E., Saborio, S., and Rovida, F. (2017). Antibody-based assay discriminates Zika virus infection from other flaviviruses. Proceedings of the National Academy of Sciences 114, 8384-8389.

Bamford, C. G., de Souza, W. M., Parry, R., and Gifford, R. J. (2022). Comparative analysis of genome-encoded viral sequences reveals the evolutionary history of flavivirids (family Flaviviridae). Virus Evolution 8, veac085.

Byrne, A. B., and Talarico, L. B. (2021). Role of the complement system in antibody-dependent enhancement of flavivirus infections. International Journal of Infectious Diseases 103, 404-411.

Cerutti, H., Tesi, G., Soldatini, C., Bandini, T., Castria, M., and Brogi, A. (2022). Development of an Anti-Zika and Anti-Dengue IgM ELISA Assay: Evaluation of cross reactivity and validation. Tropical Medicine and Infectious Disease 7, 348.

Chan, C. Y., Low, J. Z. H., Gan, E. S., Ong, E. Z., Zhang, S. L.-X., Tan, H. C., Chai, X., Ghosh, S., Ooi, E. E., and Chan, K. R. (2019). Antibody-Dependent dengue virus entry modulates cell intrinsic responses for enhanced infection. Msphere 4, 10.1128/msphere. 00528-19.

Chan, K. R., Ismail, A. A., Thergarajan, G., Raju, C. S., Yam, H. C., Rishya, M., and Sekaran, S. D. (2022). Serological cross-reactivity among common flaviviruses. Frontiers in Cellular and Infection Microbiology 12, 975398.

Chong, H. Y., Leow, C. Y., Majeed, A. B. A., and Leow, C. H. (2019). Flavivirus infection—A review of immunopathogenesis, immunological response, and immunodiagnosis. Virus research 274, 197770.

Dejnirattisai, W., Supasa, P., Wongwiwat, W., Rouvinski, A., Barba-Spaeth, G., Duangchinda, T., Sakuntabhai, A., Cao-Lormeau, V.-M., Malasit, P., and Rey, F. A. (2016). Dengue virus sero-cross-reactivity drives antibody-dependent enhancement of infection with zika virus. Nature immunology 17, 1102-1108.

Diamond, M. S. (2003). Evasion of innate and adaptive immunity by flaviviruses. Immunology and cell biology 81, 196-206.

Elong Ngono, A., and Shresta, S. (2018). Immune response to dengue and Zika. Annual review of immunology 36, 279-308.

Flipse, J., Wilschut, J., and Smit, J. M. (2013). Molecular mechanisms involved in antibody‐dependent enhancement of dengue virus infection in humans. Traffic 14, 25-35.

Gaspar-Castillo, C., Rodríguez, M. H., Ortiz-Navarrete, V., Alpuche-Aranda, C. M., and Martinez-Barnetche, J. (2023). Structural and immunological basis of cross-reactivity between dengue and Zika infections: Implications in serosurveillance in endemic regions. Frontiers in Microbiology 14, 1107496.

Gomes da Silva, P., Seixas dos Reis, J. A., Nogueira Rodrigues, M., da Silva Ardaya, Q., and Mesquita, J. R. (2023). Serological cross-reactivity in zoonotic flaviviral infections of medical importance. Antibodies 12, 18.

Halstead, S. (1970). Observations related to pathogensis of dengue hemorrhagic fever. VI. Hypotheses and discussion. The Yale journal of biology and medicine 42, 350.

Halstead, S. B. (2017). Biologic evidence required for Zika disease enhancement by dengue antibodies. Emerging Infectious Diseases 23, 569.

Hurtado‐Monzón, A. M., Cordero‐Rivera, C. D., Farfan‐Morales, C. N., Osuna‐Ramos, J. F., De Jesús‐González, L. A., Reyes‐Ruiz, J. M., and Del Ángel, R. M. (2020). The role of anti‐flavivirus humoral immune response in protection and pathogenesis. Reviews in medical virology 30, e2100.

Katzelnick, L. C., Gresh, L., Halloran, M. E., Mercado, J. C., Kuan, G., Gordon, A., Balmaseda, A., and Harris, E. (2017). Antibody-dependent enhancement of severe dengue disease in humans. Science 358, 929-932.

Langerak, T., Mumtaz, N., Tolk, V. I., van Gorp, E. C., Martina, B. E., Rockx, B., and Koopmans, M. P. (2019). The possible role of cross-reactive dengue virus antibodies in Zika virus pathogenesis. PLoS pathogens 15, e1007640.

Lee, M. F., Voon, G. Z., Lim, H. X., Chua, M. L., and Poh, C. L. (2022). Innate and adaptive immune evasion by dengue virus. Frontiers in Cellular and Infection Microbiology 12, 1004608.

Montecillo-Aguado, M. R., Montes-Gómez, A. E., García-Cordero, J., Corzo-Gómez, J., Vivanco-Cid, H., Mellado-Sánchez, G., Muñoz-Medina, J. E., Gutiérrez-Castañeda, B., Santos-Argumedo, L., and González-Bonilla, C. (2019). Cross‐reaction, enhancement, and neutralization activity of dengue virus antibodies against zika virus: a study in the Mexican population. Journal of immunology research 2019, 7239347.

Ou, T. P., Yun, C., Auerswald, H., In, S., Leang, R., Huy, R., Choeung, R., Dussart, P., and Duong, V. (2020). Improved detection of dengue and Zika viruses using multiplex RT-qPCR assays. Journal of Virological Methods 282, 113862.

Panmei, K., Hakeem, S. A., Okafor, O., Mammen, S., and Abraham, A. M. (2024). Performance evaluation of TaqMan™ Arbovirus Triplex Kit (ZIKV/DENV/CHIKV) for detection and differentiation of Dengue and Chikungunya viral RNA in serum samples of symptomatic patients. medRxiv, 2024.06. 12.24308802.

Pantoja, P., Pérez-Guzmán, E. X., Rodríguez, I. V., White, L. J., González, O., Serrano, C., Giavedoni, L., Hodara, V., Cruz, L., and Arana, T. (2017). Zika virus pathogenesis in rhesus macaques is unaffected by pre-existing immunity to dengue virus. Nature communications 8, 15674.

Pereira, S. H., Sá Magalhães Serafim, M., Moraes, T. d. F. S., Zini, N., Abrahão, J. S., Nogueira, M. L., Coelho dos Reis, J. G. A., Bagno, F. F., and da Fonseca, F. G. (2024). Design, development, and validation of multi-epitope proteins for serological diagnosis of Zika virus infections and discrimination from dengue virus seropositivity. PLOS Neglected Tropical Diseases 18, e0012100.

Priyamvada, L., Quicke, K. M., Hudson, W. H., Onlamoon, N., Sewatanon, J., Edupuganti, S., Pattanapanyasat, K., Chokephaibulkit, K., Mulligan, M. J., and Wilson, P. C. (2016). Human antibody responses after dengue virus infection are highly cross-reactive to Zika virus. Proceedings of the National Academy of Sciences 113, 7852-7857.

Rabe, I. B. (2016). Interim guidance for interpretation of Zika virus antibody test results. MMWR. Morbidity and mortality weekly report 65.

Rathore, A., and St John, A. (2020). Cross-Reactive Immunity Among Flaviviruses. Front Immunol. 2020 11: 334.

Salem, G. M., Galula, J. U., Wu, S.-R., Liu, J.-H., Chen, Y.-H., Wang, W.-H., Wang, S.-F., Song, C.-S., Chen, F.-C., and Abarientos, A. B. (2024). Antibodies from dengue patients with prior exposure to Japanese encephalitis virus are broadly neutralizing against Zika virus. Communications Biology 7, 15.

Sekaran, S. D., Ismail, A. A., Thergarajan, G., Chandramathi, S., Rahman, S. H., Mani, R. R., Jusof, F. F., Lim, Y. A., and Manikam, R. (2022). Host immune response against DENV and ZIKV infections. Frontiers in cellular and infection microbiology 12, 975222.

Sevvana, M., Rogers, T. F., Miller, A. S., Long, F., Klose, T., Beutler, N., Lai, Y.-C., Parren, M., Walker, L. M., and Buda, G. (2020). Structural basis of Zika virus specific neutralization in subsequent flavivirus infections. Viruses 12, 1346.

Shan, C., Muruato, A. E., Nunes, B. T., Luo, H., Xie, X., Medeiros, D. B., Wakamiya, M., Tesh, R. B., Barrett, A. D., and Wang, T. (2017). A live-attenuated Zika virus vaccine candidate induces sterilizing immunity in mouse models. Nature medicine 23, 763-767.

Singh, K., Martinez, M. G., Lin, J., Gregory, J., Nguyen, T. U., Abdelaal, R., Kang, K., Brennand, K., Grünweller, A., and Ouyang, Z. (2022). Transcriptional and translational dynamics of Zika and dengue virus infection. Viruses 14, 1418.

Sittikul, P., Sriburin, P., Rattanamahaphoom, J., Limkittikul, K., Sirivichayakul, C., and Chatchen, S. (2022). Combining immunoassays to identify Zika virus infection in dengue-endemic areas. Tropical Medicine and Infectious Disease 7, 254.

Slon Campos, J. L., Mongkolsapaya, J., and Screaton, G. R. (2018). The immune response against flaviviruses. Nature immunology 19, 1189-1198.

Tan, T. Y., Fibriansah, G., Kostyuchenko, V. A., Ng, T.-S., Lim, X.-X., Zhang, S., Lim, X.-N., Wang, J., Shi, J., and Morais, M. C. (2020). Capsid protein structure in Zika virus reveals the flavivirus assembly process. Nature communications 11, 895.

Tirado, S. M. C., and Yoon, K.-J. (2003). Antibody-dependent enhancement of virus infection and disease. Viral immunology 16, 69-86.

Uhuami, A. O., Bello, M. B., and Imam, M. U. (2024). FLAVIVIRUS CROSS-REACTIVITY: INSIGHTS INTO E-PROTEIN CONSERVANCY, PRE-EXISTING IMMUNITY, AND CO-INFECTION. The Microbe, 100105.

Zhao, R., Wang, M., Cao, J., Shen, J., Zhou, X., Wang, D., and Cao, J. (2021). Flavivirus: from structure to therapeutics development. Life 11, 615.