Parvovirus B19 NS1 protein induces synovitis mimicking rheumatoid arthritis

Abstract This study aims to investigate the role of parvovirus B19 infection in the pathogenesis of rheumatoid arthritis (RA). B19-NS1 DNA was cloned into the LentiORF pLEX-MCS vector, then co-transfected with the pLEX-MCS-NS1 vector and packaging system to produce LEX-NS1 lentiviral stock. LEX was...

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Main Authors: Chang-Yi Yen, Chia-Chun Tseng, Chia‐Hui Lin, Yuan‐Zhao Lin, Ruei‐Nian Li, Pin-Yi Wang, Kuan-Yu Chen, Cheng-Chin Wu, Tsan-Teng Ou, Chung-Jen Chen, Yu-Peng Liu, Jeng-Hsien Yen
Format: Article
Language:English
Published: Nature Portfolio 2025-08-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-11900-3
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author Chang-Yi Yen
Chia-Chun Tseng
Chia‐Hui Lin
Yuan‐Zhao Lin
Ruei‐Nian Li
Pin-Yi Wang
Kuan-Yu Chen
Cheng-Chin Wu
Tsan-Teng Ou
Chung-Jen Chen
Yu-Peng Liu
Jeng-Hsien Yen
author_facet Chang-Yi Yen
Chia-Chun Tseng
Chia‐Hui Lin
Yuan‐Zhao Lin
Ruei‐Nian Li
Pin-Yi Wang
Kuan-Yu Chen
Cheng-Chin Wu
Tsan-Teng Ou
Chung-Jen Chen
Yu-Peng Liu
Jeng-Hsien Yen
author_sort Chang-Yi Yen
collection DOAJ
description Abstract This study aims to investigate the role of parvovirus B19 infection in the pathogenesis of rheumatoid arthritis (RA). B19-NS1 DNA was cloned into the LentiORF pLEX-MCS vector, then co-transfected with the pLEX-MCS-NS1 vector and packaging system to produce LEX-NS1 lentiviral stock. LEX was also prepared as the control. Transduction of LEX-NS1 or LEX lentivirus into the SW982 cell line then proceeded, and total RNA was extracted for RNA-seq. Pathway analysis and comparison of pathway status between this study and GEO datasets were performed, demonstrating that acute phase response signaling, NRF2-mediated oxidative stress response, and mTOR signaling pathways were activated after the transduction of LEX-NS1 into the SW982 cell line, although the interferon signaling pathway was inhibited. The comparison of all pathways using hierarchical clustering showed that the pathway status after transduction of B19-NS1 was closer to RA than that in osteoarthritis. Similar findings can also be found in cellular immune, humoral immune, cytokine, apoptosis, cellular growth, cellular stress, growth factor, and intracellular pathways. In conclusion, parvovirus B19-NS1 can induce inflammation of the synovium mimicking synovitis in RA; therefore, parvovirus B19 infection might be one of the trigger factors in the pathogenesis of RA.
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spelling doaj-art-2079ee8908bc421fb1866c0dbfd2c2ba2025-08-20T04:03:02ZengNature PortfolioScientific Reports2045-23222025-08-0115111110.1038/s41598-025-11900-3Parvovirus B19 NS1 protein induces synovitis mimicking rheumatoid arthritisChang-Yi Yen0Chia-Chun Tseng1Chia‐Hui Lin2Yuan‐Zhao Lin3Ruei‐Nian Li4Pin-Yi Wang5Kuan-Yu Chen6Cheng-Chin Wu7Tsan-Teng Ou8Chung-Jen Chen9Yu-Peng Liu10Jeng-Hsien Yen11Division of Rheumatology, Department of Internal Medicine, Kaohsiung Medical University HospitalDivision of Rheumatology, Department of Internal Medicine, Kaohsiung Medical University HospitalDivision of Rheumatology, Department of Internal Medicine, Kaohsiung Medical University HospitalDivision of Rheumatology, Department of Internal Medicine, Kaohsiung Medical University HospitalDepartment of Biomedical Science and Environmental Biology, College of Life Science, Kaohsiung Medical UniversityDepartment of Internal Medicine, Kaohsiung Municipal Siaogang HospitalGraduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical UniversityDivision of Rheumatology, Department of Internal Medicine, Kaohsiung Medical University HospitalDivision of Rheumatology, Department of Internal Medicine, Kaohsiung Medical University HospitalDivision of Rheumatology, Department of Internal Medicine, Kaohsiung Medical University HospitalGraduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical UniversityDivision of Rheumatology, Department of Internal Medicine, Kaohsiung Medical University HospitalAbstract This study aims to investigate the role of parvovirus B19 infection in the pathogenesis of rheumatoid arthritis (RA). B19-NS1 DNA was cloned into the LentiORF pLEX-MCS vector, then co-transfected with the pLEX-MCS-NS1 vector and packaging system to produce LEX-NS1 lentiviral stock. LEX was also prepared as the control. Transduction of LEX-NS1 or LEX lentivirus into the SW982 cell line then proceeded, and total RNA was extracted for RNA-seq. Pathway analysis and comparison of pathway status between this study and GEO datasets were performed, demonstrating that acute phase response signaling, NRF2-mediated oxidative stress response, and mTOR signaling pathways were activated after the transduction of LEX-NS1 into the SW982 cell line, although the interferon signaling pathway was inhibited. The comparison of all pathways using hierarchical clustering showed that the pathway status after transduction of B19-NS1 was closer to RA than that in osteoarthritis. Similar findings can also be found in cellular immune, humoral immune, cytokine, apoptosis, cellular growth, cellular stress, growth factor, and intracellular pathways. In conclusion, parvovirus B19-NS1 can induce inflammation of the synovium mimicking synovitis in RA; therefore, parvovirus B19 infection might be one of the trigger factors in the pathogenesis of RA.https://doi.org/10.1038/s41598-025-11900-3Parvovirus B19Rheumatoid arthritisSynovitisRNA-seq
spellingShingle Chang-Yi Yen
Chia-Chun Tseng
Chia‐Hui Lin
Yuan‐Zhao Lin
Ruei‐Nian Li
Pin-Yi Wang
Kuan-Yu Chen
Cheng-Chin Wu
Tsan-Teng Ou
Chung-Jen Chen
Yu-Peng Liu
Jeng-Hsien Yen
Parvovirus B19 NS1 protein induces synovitis mimicking rheumatoid arthritis
Scientific Reports
Parvovirus B19
Rheumatoid arthritis
Synovitis
RNA-seq
title Parvovirus B19 NS1 protein induces synovitis mimicking rheumatoid arthritis
title_full Parvovirus B19 NS1 protein induces synovitis mimicking rheumatoid arthritis
title_fullStr Parvovirus B19 NS1 protein induces synovitis mimicking rheumatoid arthritis
title_full_unstemmed Parvovirus B19 NS1 protein induces synovitis mimicking rheumatoid arthritis
title_short Parvovirus B19 NS1 protein induces synovitis mimicking rheumatoid arthritis
title_sort parvovirus b19 ns1 protein induces synovitis mimicking rheumatoid arthritis
topic Parvovirus B19
Rheumatoid arthritis
Synovitis
RNA-seq
url https://doi.org/10.1038/s41598-025-11900-3
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