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Peer-reviewedCC BY 4.0Frontiers in Immunology

Single‐cell transcriptomic analysis of the immune response to CHIKV infection

8 affiliations
  1. 1Women and Children Medical Research Center, Affiliated Foshan Women and Children Hospital, Guangdong Medical University
  2. 2School of Pharmaceutical Sciences, Southern Medical University, Southern Medical University
  3. 3Biobank, Affiliated Foshan Women and Children Hospital, Guangdong Medical University
  4. 4Foshan Key Laboratory of Stem Cell and Maternal-Child Health, Foshan Women and Children Hospital
  5. 5Internal Medicine Department, Affiliated Foshan Women and Children Hospital, Guangdong Medical University
  6. 6Shenzhen Digital Cloud Valley Biotechnology Co., Ltd
  7. 7Emergency Department, Affiliated Foshan Women and Children Hospital, Guangdong Medical University
  8. 8Geriatric Department, Affiliated Foshan Women and Children Hospital, Guangdong Medical University

Abstract

Background: The Chikungunya virus (CHIKV), a re-emerging mosquito-borne alphavirus, is responsible for acute febrile illness and severe polyarthralgia. Although both innate and adaptive immune responses influence the disease outcomes, the detailed cellular immunopathogenesis of CHIKV in peripheral blood is not yet fully elucidated.

Methods: We profiled PBMCs from 29 patients with acute CHIKV infection and 10 controls via single-cell RNA sequencing. Between-group analyses treated donors as biological replicates, incorporating pseudobulk differential expression analysis as well as donor-level comparisons of pathway scores and cell proportions. Orthogonal validation was performed using qPCR and ELISA, and an exploratory analysis was conducted on a publicly available DENV dataset.

Results: Interferon-response signatures were upregulated across the majority of PBMC populations, with particularly prominent signals observed in monocytes and NK cells. Differences in relative cell composition were detected in descriptive statistics, but did not retain statistical significance after donor-level multiple testing correction. B-cell immunoglobulin isotypes varied across cell subsets, and their transcripts did not allow determination of antigen specificity. Cross-study analysis of DENV did not support the quantitative conclusion that the CHIKV-induced immune response is stronger.

Conclusions: Acute CHIKV infection is associated with a broad interferon-stimulated transcriptional program in PBMCs. Conclusions drawn from cross-sectional and cross-study comparisons require cautious interpretation.

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BibTeX
@article{huang2026singlecell,
  title = {{Single‐cell transcriptomic analysis of the immune response to CHIKV infection}},
  author = {Peng Huang and Huiyi Wang and Siya Xu and Miaogen Li and Mingjuan Guo and Haiyan Wang and Xiaoyan Gou and Can Wang and Yanjun He and Wei Pan},
  journal = {Frontiers in Immunology},
  year = {2026},
  month = oct,
  doi = {10.3389/fimmu.2026.1979359},
  url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1979359/full},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Single‐cell transcriptomic analysis of the immune response to CHIKV infection
AU  - Peng Huang
AU  - Huiyi Wang
AU  - Siya Xu
AU  - Miaogen Li
AU  - Mingjuan Guo
AU  - Haiyan Wang
AU  - Xiaoyan Gou
AU  - Can Wang
AU  - Yanjun He
AU  - Wei Pan
PY  - 2026
DA  - 2026/10/29
JO  - Frontiers in Immunology
DO  - 10.3389/fimmu.2026.1979359
UR  - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1979359/full
AB  - Background: The Chikungunya virus (CHIKV), a re-emerging mosquito-borne alphavirus, is responsible for acute febrile illness and severe polyarthralgia. Although both innate and adaptive immune responses influence the disease outcomes, the detailed cellular immunopathogenesis of CHIKV in peripheral blood is not yet fully elucidated.  Methods: We profiled PBMCs from 29 patients with acute CHIKV infection and 10 controls via single-cell RNA sequencing. Between-group analyses treated donors as biological replicates, incorporating pseudobulk differential expression analysis as well as donor-level comparisons of pathway scores and cell proportions. Orthogonal validation was performed using qPCR and ELISA, and an exploratory analysis was conducted on a publicly available DENV dataset.  Results: Interferon-response signatures were upregulated across the majority of PBMC populations, with particularly prominent signals observed in monocytes and NK cells. Differences in relative cell composition were detected in descriptive statistics, but did not retain statistical significance after donor-level multiple testing correction. B-cell immunoglobulin isotypes varied across cell subsets, and their transcripts did not allow determination of antigen specificity. Cross-study analysis of DENV did not support the quantitative conclusion that the CHIKV-induced immune response is stronger.  Conclusions: Acute CHIKV infection is associated with a broad interferon-stimulated transcriptional program in PBMCs. Conclusions drawn from cross-sectional and cross-study comparisons require cautious interpretation.
SN  - 1664-3224
ER  -