Early transcriptional signature in chikungunya predicts chronic arthralgia and reveals deficient antiviral response.

Authors

Thiago Cerqueira-Silva, Laise de Moraes, Blenda de Jesus Pereira, Jessica Silva, Cibele Orge, Kevan Akrami, Ligia Souza, Laila Horta, Moacyr Rego, Amanda Albuquerque, Joyce Karoline da Silva, Paula M Cassais, Luciano Pamplona Calvacanti, Cristina Ribeiro Cardoso, Pablo Ivan P Ramos, Luciane Amorim Santos, Manoel Barral-Netto, Aldina Barral, Ricardo Khouri, Viviane S Boaventura

Published in

The Journal of infectious diseases. Jul 21, 2026. Epub Jul 21, 2026.

Abstract

Post-acute viral syndromes are increasingly recognised as causes of prolonged disability, with a notably higher prevalence in women. This study investigated the immune signature of individuals who progressed to chronic chikungunya (CC), a condition characterised by persistent arthralgia and examined the role of biological sex in disease outcomes.
We analysed peripheral blood mononuclear cells from patients, recruited between 2016 and 2020, sampled within seven days of disease onset. The study compared patients who eventually recovered (RC, n = 11) with those who progressed to CC (n = 24), alongside nine healthy controls. We identified differentially expressed genes using bulk RNA-Seq and validated key findings by qRT-PCR and flow cytometry.
Ten genes were differentially expressed between CC and RC. Specifically, IKZF2 was upregulated in CC patients, which was validated by qRT-PCR. Conversely, ACKR3 was upregulated in RC patients, a finding validated by flow cytometry. Furthermore, CC cases demonstrated higher viral loads and downregulation of IFN-α and IFN-γ pathways compared to RC. We also found that immune profiles differed between men and women; specifically, IFNα and IFN-γ and TNF signalling pathways were upregulated in women with CC but downregulated in men with CC relative to recovered individuals.
Our findings suggest that progression to chronic chikungunya is influenced by an impaired early antiviral response combined with sex-specific immune regulation. Furthermore, ACKR3 and IKZF2 were identified as potential prognostic biomarkers for chronic chikungunya. These biomarkers may enable early identification of patients at risk of chronic disease, informing timely intervention strategies.

PMID:
42478964
Bibliographic data and abstract were imported from PubMed on 21 Jul 2026.

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