Transcriptomic insights into early mechanisms underlying 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.