Journal Article

Transcriptomic insights into early mechanisms underlying post-chikungunya chronic inflammatory joint disease

Cabral, Milena Gomes, Nakaya, Helder I., da Fonseca, Guilherme Cordenonsi, Côrtes, Marina Farrel, Vasconcelos, Ana Tereza R., Sabino, Ester Cerdeira, Ramundo, Mariana Severo, Manuli, Erika Regina, Brasil, Patrícia, da Silveira Bressan, Clarisse, Ten-Caten, Felipe, Brustolini, Otavio, Dos Santos Lázari, Carolina, Guimarães, Ana Paula, Paranhos-Baccalà, Gláucia, Gerber, Alexandra L., Pereira, Geovana Maria

2025

Overview

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.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 631/114 / 631/553 / 692/4023 / 692/420 / 692/699 / Adult / Antiviral drugs / Chikungunya / Chikungunya Fever - complications / Chikungunya Fever - genetics / Chikungunya Fever - virology / Chikungunya prognosis / Chikungunya virus / CHIKV / Chronic Disease / Chronic infection / Down-regulation / Female / Gene Expression Profiling / Humanities and Social Sciences / Humans / Immune response / Joint diseases / Joint Diseases - etiology / Joint Diseases - genetics / Male / MicroRNAs - genetics / Middle Aged / Molecular modelling / multidisciplinary / Neutrophil collagenase / Post-Chikungunya Chronic Inflammatory Joint Disease / Science / Science (multidisciplinary) / Small RNA sequencing / Total RNA sequencing / Transcriptome / Transcriptomics / Vector-borne diseases