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

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.

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Publication Details

Journal
Nature Communications
Published
2025-03-25
DOI
https://doi.org/10.1038/s41467-025-57977-2
Citations
6
Primary Topic
Mosquito-borne diseases and control
Type
article
Field-Weighted Citation Impact
11.27

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article

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

Emilie Branche, Jialei Xie, Hsueh-Han Lu, Karla M. Viramontes et al.
6 citations
Nature Communications
Mosquito-borne diseases and control
11.27
article

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

Emilie Branche, Jialei Xie, Hsueh-Han Lu, Karla M. Viramontes, Aaron F. Carlin, Alex E. Clark, Rachel E. McMillan, Qin Hui Li, Sujan Shresta, Fernanda Ana‐Sosa‐Batiz, Christopher Benner, Joan M. Valls Cuevas, Rúbens Prince dos Santos Alves, Ying-Ting Wang, Sven Heinz, Aaron F. Garretson
article en
6 citations

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.

Nature CommunicationsVol. 16(1)
La Jolla Institute for Immunology (US), UC San Diego Health System (US), University of California San Diego (US)
Burroughs Wellcome Fund, American Association of Immunologists, Ministry of Science and Technology, Taiwan
Good health and well-being
Openalex Percentile: Top 2%
Mosquito-borne diseases and control
11.27
DOIOpen Access PDFOpenAlex
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