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Zika but not Dengue virus infection limits NF-κB activity in human monocyte-derived dendritic cells and suppresses their ability to activate T cells

Author

Listed:
  • Ying-Ting Wang

    (La Jolla Institute for Immunology)

  • Emilie Branche

    (La Jolla Institute for Immunology)

  • Jialei Xie

    (San Diego)

  • Rachel E. McMillan

    (San Diego
    La Jolla)

  • Fernanda Ana-Sosa-Batiz

    (La Jolla Institute for Immunology)

  • Hsueh-Han Lu

    (La Jolla Institute for Immunology
    La Jolla)

  • Qin Hui Li

    (La Jolla Institute for Immunology
    La Jolla)

  • Alex E. Clark

    (San Diego)

  • Joan M. Valls Cuevas

    (La Jolla Institute for Immunology)

  • Karla M. Viramontes

    (La Jolla Institute for Immunology)

  • Aaron F. Garretson

    (San Diego)

  • Rúbens Prince Santos Alves

    (La Jolla Institute for Immunology)

  • Sven Heinz

    (San Diego)

  • Christopher Benner

    (San Diego)

  • Aaron F. Carlin

    (San Diego
    San Diego)

  • Sujan Shresta

    (La Jolla Institute for Immunology
    San Diego)

Abstract

Understanding flavivirus immunity is critical for the development of pan-flavivirus vaccines. Dendritic cells (DC) coordinate antiviral innate and adaptive immune responses, and they can be targeted by flaviviruses as a mechanism of immune evasion. Using an unbiased genome-wide approach designed to specifically identify flavivirus-modulated pathways, we found that, while dengue virus (DENV) robustly activates DCs, Zika virus (ZIKV) causes minimal activation of genes involved in DC activation, maturation, and antigen presentation, reducing cytokine secretion and the stimulation of allogeneic and peptide-specific T cell responses. Mechanistically, ZIKV inhibits DC maturation by suppressing NF-κB p65 recruitment and the subsequent transcription of proinflammatory and DC maturation-related genes. Thus, we identify a divergence in the effects of ZIKV and DENV on the host T cell response, highlighting the need to factor such differences into the design of anti-flavivirus vaccines.

Suggested Citation

  • Ying-Ting Wang & Emilie Branche & Jialei Xie & Rachel E. McMillan & Fernanda Ana-Sosa-Batiz & Hsueh-Han Lu & Qin Hui Li & Alex E. Clark & Joan M. Valls Cuevas & Karla M. Viramontes & Aaron F. Garretso, 2025. "Zika but not Dengue virus infection limits NF-κB activity in human monocyte-derived dendritic cells and suppresses their ability to activate T cells," Nature Communications, Nature, vol. 16(1), pages 1-14, December.
  • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-57977-2
    DOI: 10.1038/s41467-025-57977-2
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    References listed on IDEAS

    as
    1. Emilie Branche & Ying-Ting Wang & Karla M. Viramontes & Joan M. Valls Cuevas & Jialei Xie & Fernanda Ana-Sosa-Batiz & Norazizah Shafee & Sascha H. Duttke & Rachel E. McMillan & Alex E. Clark & Michael, 2022. "SREBP2-dependent lipid gene transcription enhances the infection of human dendritic cells by Zika virus," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    2. Ryan D. Pardy & Stefanie F. Valbon & Brendan Cordeiro & Connie M. Krawczyk & Martin J. Richer, 2021. "An epidemic Zika virus isolate suppresses antiviral immunity by disrupting antigen presentation pathways," Nature Communications, Nature, vol. 12(1), pages 1-16, December.
    3. repec:plo:ppat00:1007821 is not listed on IDEAS
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