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Transcriptomic analysis of chronic chikungunya in the Reunionese CHIKGene cohort uncovers a shift in gene expression more than 10 years after infection
P. Gérardin, R. Medina-Santos, S. Le Clerc, L. Bruneau, A. Maillot, T. Labib, M. Rahmouni, JL. Spadoni, JP. Meyniel, C. Cornet, C. Lefebvre, N. El Jahrani, J. Savara, MJ. Mathew, C. Fontaine, C. Payet, N. Ah-You, C. Chabert, C. Mussard, S....
Jazyk angličtina Země Nizozemsko
Typ dokumentu časopisecké články
NLK
Directory of Open Access Journals
od 2023
ProQuest Central
od 2003-02-01 do Před 2 měsíci
Nursing & Allied Health Database (ProQuest)
od 2003-02-01 do Před 2 měsíci
Health & Medicine (ProQuest)
od 2003-02-01 do Před 2 měsíci
Health Management Database (ProQuest)
od 2003-02-01 do Před 2 měsíci
Public Health Database (ProQuest)
od 2003-02-01 do Před 2 měsíci
ROAD: Directory of Open Access Scholarly Resources
od 2003
- MeSH
- chronická nemoc MeSH
- dospělí MeSH
- horečka chikungunya * genetika epidemiologie virologie MeSH
- kohortové studie MeSH
- leukocyty mononukleární MeSH
- lidé středního věku MeSH
- lidé MeSH
- senioři MeSH
- stanovení celkové genové exprese MeSH
- transkriptom * MeSH
- virus chikungunya MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Réunion MeSH
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.
Department of Computer Science VSB Technical University of Ostrava Ostrava Czech Republic
Department of Immunology Palacky University and University Hospital Olomouc Czech Republic
École d'Ingénieurs Généraliste du Numérique EFREI Paris France
Citace poskytuje Crossref.org
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