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Comparing human pediatric immune responses to primary infection with dengue, chikungunya and Zika viruses

Lewis E Tomalin1, Sandra Bos2, Rafael Fenutria3

  • 1Department of Population Health and Science Policy, Icahn School of Medicine at Mount Sinai, New York, NY, United States.

Frontiers in Immunology
|December 5, 2025
PubMed

Insights

Children’s immune responses to dengue virus (DENV), Zika virus (ZIKV), and chikungunya virus (CHIKV) differ significantly. ZIKV infection showed a distinct, delayed immune response compared to DENV and CHIKV, highlighting virus-specific immunological signatures.

Area of Science:

  • Virology
  • Immunology
  • Pediatrics

Background:

  • Dengue virus (DENV), Zika virus (ZIKV), and chikungunya virus (CHIKV) are prevalent arboviruses with similar transmission cycles, posing a global health risk.
  • Overlapping clinical presentations of DENV, ZIKV, and CHIKV infections obscure distinct immune mechanisms, especially in children.
  • Understanding virus-specific immune signatures in pediatric populations is crucial for accurate diagnosis and treatment.

Purpose of the Study:

  • To characterize and compare the immune responses to DENV, ZIKV, and CHIKV in children.
  • To identify specific immunological signatures associated with each arbovirus infection.
  • To elucidate how viral taxonomy relates to distinct immune responses in pediatric patients.

Main Methods:

  • Analysis of cytokine, chemokine, and growth factor profiles in plasma/serum from infected children.
  • Assessment of immune cell profiles in peripheral blood mononuclear cells (PBMCs).
  • Comparison of immune responses during acute (days 1-6) and recovery (days 14-25) phases of primary DENV1/DENV3, ZIKV, or CHIKV infection.

Main Results:

  • Chikungunya virus (CHIKV) and dengue virus (DENV) elicited similar innate immune responses, characterized by acute cytokine concentrations and monocyte frequencies.
  • Zika virus (ZIKV) infection resulted in a mild innate response and a delayed adaptive response with attenuated cytokine production and T/B cell activation.
  • ZIKV exhibited a distinct immune profile, including rapid B cell expansion but delayed activation, differentiating it from DENV despite both being flaviviruses.

Conclusions:

  • Early immune responses to arboviruses are dictated by infection-specific dynamics rather than solely by viral taxonomy.
  • Distinct immunological signatures characterize DENV, ZIKV, and CHIKV infections in children.
  • Findings underscore the importance of considering virus-specific immune profiles for understanding arbovirus pathogenesis.
Abstract

Keywords:
alphavirusarboviruscytokineflavivirusimmune responsemass cytometry (CyTOF)multiomic analyses

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