Transcriptomic insights into early mechanisms underlying post-chikungunya chronic inflammatory joint disease
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 molecu...
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Nature Portfolio
2025-02-01
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| Online Access: | https://doi.org/10.1038/s41598-025-86761-x |
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| author | Mariana Severo Ramundo Guilherme Cordenonsi da Fonseca Felipe Ten-Caten Alexandra L. Gerber Ana Paula Guimarães Erika Regina Manuli Marina Farrel Côrtes Geovana Maria Pereira Otavio Brustolini Milena Gomes Cabral Carolina Dos Santos Lázari Patrícia Brasil Clarisse da Silveira Bressan Helder I. Nakaya Gláucia Paranhos-Baccalà Ana Tereza R. Vasconcelos Ester Cerdeira Sabino |
| author_facet | Mariana Severo Ramundo Guilherme Cordenonsi da Fonseca Felipe Ten-Caten Alexandra L. Gerber Ana Paula Guimarães Erika Regina Manuli Marina Farrel Côrtes Geovana Maria Pereira Otavio Brustolini Milena Gomes Cabral Carolina Dos Santos Lázari Patrícia Brasil Clarisse da Silveira Bressan Helder I. Nakaya Gláucia Paranhos-Baccalà Ana Tereza R. Vasconcelos Ester Cerdeira Sabino |
| author_sort | Mariana Severo Ramundo |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-c5d4b20cd83c4eeba9d4bbaa7ba1ad60 |
| institution | OA Journals |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Nature Portfolio |
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| series | Scientific Reports |
| spelling | doaj-art-c5d4b20cd83c4eeba9d4bbaa7ba1ad602025-08-20T02:16:54ZengNature PortfolioScientific Reports2045-23222025-02-0115111410.1038/s41598-025-86761-xTranscriptomic insights into early mechanisms underlying post-chikungunya chronic inflammatory joint diseaseMariana Severo Ramundo0Guilherme Cordenonsi da Fonseca1Felipe Ten-Caten2Alexandra L. Gerber3Ana Paula Guimarães4Erika Regina Manuli5Marina Farrel Côrtes6Geovana Maria Pereira7Otavio Brustolini8Milena Gomes Cabral9Carolina Dos Santos Lázari10Patrícia Brasil11Clarisse da Silveira Bressan12Helder I. Nakaya13Gláucia Paranhos-Baccalà14Ana Tereza R. Vasconcelos15Ester Cerdeira Sabino16Departamento de Clínica Médica, Faculdade de Medicina, Universidade de São PauloLABINFO, Laboratório Nacional de Computação CientíficaDepartamento de Moléstias Infecciosas e Parasitárias e Instituto de Medicina Tropical, Faculdade de Medicina, Universidade de São PauloLABINFO, Laboratório Nacional de Computação CientíficaLABINFO, Laboratório Nacional de Computação CientíficaDepartamento de Moléstias Infecciosas e Parasitárias e Instituto de Medicina Tropical, Faculdade de Medicina, Universidade de São PauloDepartamento de Moléstias Infecciosas e Parasitárias e Instituto de Medicina Tropical, Faculdade de Medicina, Universidade de São PauloDepartamento de Moléstias Infecciosas e Parasitárias e Instituto de Medicina Tropical, Faculdade de Medicina, Universidade de São PauloLABINFO, Laboratório Nacional de Computação CientíficaDepartamento de Moléstias Infecciosas e Parasitárias e Instituto de Medicina Tropical, Faculdade de Medicina, Universidade de São PauloFleury Medicina e SaúdeInstituto Nacional de Infectologia Evandro Chagas, Fundação Oswaldo CruzInstituto Nacional de Infectologia Evandro Chagas, Fundação Oswaldo CruzScientific Platform Pasteur, Universidade de São PauloGlobal Medical Affairs Department, bioMérieux SALABINFO, Laboratório Nacional de Computação CientíficaLaboratorio de Investigaçao Medica LIM-46, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao PauloAbstract 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.https://doi.org/10.1038/s41598-025-86761-xCHIKVChikungunyaPost-Chikungunya Chronic Inflammatory Joint DiseaseTotal RNA sequencingSmall RNA sequencingChikungunya prognosis |
| spellingShingle | Mariana Severo Ramundo Guilherme Cordenonsi da Fonseca Felipe Ten-Caten Alexandra L. Gerber Ana Paula Guimarães Erika Regina Manuli Marina Farrel Côrtes Geovana Maria Pereira Otavio Brustolini Milena Gomes Cabral Carolina Dos Santos Lázari Patrícia Brasil Clarisse da Silveira Bressan Helder I. Nakaya Gláucia Paranhos-Baccalà Ana Tereza R. Vasconcelos Ester Cerdeira Sabino Transcriptomic insights into early mechanisms underlying post-chikungunya chronic inflammatory joint disease Scientific Reports CHIKV Chikungunya Post-Chikungunya Chronic Inflammatory Joint Disease Total RNA sequencing Small RNA sequencing Chikungunya prognosis |
| title | Transcriptomic insights into early mechanisms underlying post-chikungunya chronic inflammatory joint disease |
| title_full | Transcriptomic insights into early mechanisms underlying post-chikungunya chronic inflammatory joint disease |
| title_fullStr | Transcriptomic insights into early mechanisms underlying post-chikungunya chronic inflammatory joint disease |
| title_full_unstemmed | Transcriptomic insights into early mechanisms underlying post-chikungunya chronic inflammatory joint disease |
| title_short | Transcriptomic insights into early mechanisms underlying post-chikungunya chronic inflammatory joint disease |
| title_sort | transcriptomic insights into early mechanisms underlying post chikungunya chronic inflammatory joint disease |
| topic | CHIKV Chikungunya Post-Chikungunya Chronic Inflammatory Joint Disease Total RNA sequencing Small RNA sequencing Chikungunya prognosis |
| url | https://doi.org/10.1038/s41598-025-86761-x |
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