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. 2025 May-Jun:65:102825.
doi: 10.1016/j.tmaid.2025.102825. Epub 2025 Feb 23.

Transcriptomic analysis of chronic chikungunya in the Reunionese CHIKGene cohort uncovers a shift in gene expression more than 10 years after infection

Patrick Gérardin  1 , Raissa Medina-Santos  2 , Sigrid Le Clerc  3 , Léa Bruneau  4 , Adrien Maillot  5 , Taoufik Labib  3 , Myriam Rahmouni  3 , Jean-Louis Spadoni  3 , Jean-Philippe Meyniel  6 , Clémence Cornet  7 , Cécile Lefebvre  8 , Nora El Jahrani  8 , Jakub Savara  9 , Mano Joseph Mathew  10 , Christine Fontaine  11 , Christine Payet  11 , Nathalie Ah-You  11 , Cécile Chabert  11 , Corinne Mussard  12 , Sylvaine Porcherat  12 , Samir Medjane  13 , Josselin Noirel  3 , Catherine Marimoutou  4 , Hakim Hocini  8 , Jean-François Zagury  14
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Free article

Transcriptomic analysis of chronic chikungunya in the Reunionese CHIKGene cohort uncovers a shift in gene expression more than 10 years after infection

Patrick Gérardin et al. Travel Med Infect Dis. 2025 May-Jun.
Free article

Abstract

Aim: In 2005-2006, a chikungunya epidemic of unprecedented magnitude hit Reunion Island, which raised a public health concern through the substantial proportions of long-lasting manifestations. To understand the pathophysiology underlying chronic chikungunya (CC), we designed the CHIKGene cohort study and collected blood samples from 133 subjects diagnosed with CC and from 86 control individuals that had recovered within 3 months, 12-to-15 years after exposure.

Methods: We conducted bulk RNAseq analysis on peripheral blood mononuclear cells to find differentially expressed genes (DEGs), gene set enrichment analysis (GSEA) and gene ontologies to uncover top-level enriched terms associated with DEGs, and weighted gene correlation network analysis (WGCNA) to elucidate underlying cellular processes.

Results: Among 1549 DEGs, gene expression analysis identified 10 top genes including NR4A2 and TRIM58 (upregulated in CC), IGHG3 and IGHV3-49 (downregulated in CC) linked to immune regulation, OSBP2 (upregulated in CC) and SEMA6B (downregulated in CC) linked to neuronal homeostasis and axon guidance, respectively. GSEA and WGCNA unveiled cellular processes such as "Metabolism of RNA" and "Cell Cycle".

Conclusions: This study uncovers a shift in gene expression of CC subjects. IGHG3 and IGHV3-49 gene shut-offs spotlight the importance of neutralizing antibodies against chikungunya virus in the progression to chronic disease. Human diseases associations highlight connections to rheumatoid arthritis, nervous and cardiac systems. GSEA and WGCNA bounce the hypotheses of a persistent viral reservoir or an increased susceptibility to RNA viral pathogens with new onset infections. Together, our findings might offer potential targets for therapeutic options aimed at alleviating chronic chikungunya.

Keywords: Chronic disease; Gene expression; RNAseq; Rheumatoid arthritis; Transcriptomics; chikungunya.

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Conflict of interest statement

Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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