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Updated: May 25, 2025
High-Throughput Transcriptome Analysis for Investigating Host-Pathogen Interactions
Published on: March 5, 2022
Transcriptomic insights into early mechanisms underlying post-chikungunya chronic inflammatory joint disease
Mariana Severo Ramundo1,2, Guilherme Cordenonsi da Fonseca3, Felipe Ten-Caten4,5
1Departamento de Clínica Médica, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil. marianasevero@usp.br.
Insights
Chikungunya virus infection can lead to chronic joint disease. This study identified molecular signatures in early disease phases, revealing immune dysregulation linked to persistent inflammation and potential therapeutic targets for post-chikungunya chronic inflammatory joint disease.
Area of Science:
- Virology
- Immunology
- Genomics
Background:
- Chikungunya virus (CHIKV) infection frequently causes Post-Chikungunya Chronic Inflammatory Joint Disease (pCHIKV-CIJD), impacting daily life and healthcare costs.
- Understanding the molecular basis of pCHIKV-CIJD is crucial for developing effective management strategies.
Purpose of the Study:
- To investigate the molecular mechanisms underlying the development of pCHIKV-CIJD.
- To identify molecular signatures associated with disease chronification in CHIKV-infected patients.
Main Methods:
- Analysis of RNA transcripts, including small RNAs, from whole blood of CHIKV-infected patients.
- Comparison of molecular profiles between patients who developed pCHIKV-CIJD and those who did not.
Main Results:
- Identified molecular signatures linked to immune response dysregulation in pCHIKV-CIJD development.
- Observed down-regulation of LIFR and up-regulation of hsa-miR-98-5p in the acute phase of pCHIKV-CIJD.
- Found reduced transcript levels of antiviral response genes (MMP8, LFT, DDIT4) in pCHIKV-CIJD patients, potentially promoting virus persistence.
Conclusions:
- Early molecular events, particularly immune dysregulation, are associated with pCHIKV-CIJD chronification.
- Identified potential molecular targets, including LIFR and hsa-miR-98-5p, for further investigation in pCHIKV-CIJD.
- Findings provide insights into the pathogenesis of chronic inflammatory arthritis post-CHIKV infection.
Abstract:
Chikungunya virus (CHIKV) infection often results in a chronic joint condition known as Post-Chikungunya Chronic Inflammatory Joint Disease (pCHIKV-CIJD). This condition disrupts individuals' daily lives and contributes to increased healthcare expenditure. This study investigated the molecular mechanisms underlying pCHIKV-CIJD development by analyzing RNA transcripts, including small RNAs, of whole blood from CHIKV-infected patients. By comparing patients who evolved to pCHIKV-CIJD with those who did not, we identified molecular signatures associated with chronification in acute and post-acute disease phases. These molecules were primarily associated with an altered immune response regulation. Notably, LIFR, an immune receptor that enhanced IL-6 transcription, was down-regulated in the acute phase of pCHIKV-CIJD patients, while its inhibitor, hsa-miR-98-5p, was up-regulated in these individuals. Other downregulated genes include members of immune mechanisms whose impairment can lead to a reduction in the first line of antiviral response, thereby promoting virus persistence for a longer period in these patients. Additionally, pCHIKV-CIJD patients exhibited reduced transcript levels of MMP8, LFT, and DDIT4, genes already implicated in the pathological process of other types of inflammatory arthritis and seemingly relevant for pCHIKV-CIJD development. Overall, our findings provide insights into the early molecular mechanisms involved in the chronification and highlight potential targets for further investigation.
