A Kaposi’s sarcoma-associated herpes virus-encoded microRNA contributes to dilated cardiomyopathy
Abstract Dilated cardiomyopathy (DCM) is the leading cause of heart transplantation. By microRNA (miRNA) array, a Kaposi’s sarcoma-associated herpes virus (KSHV)-encoded miRNA, kshv-miR-K12-1-5p, was detected in patients with DCM. The KSHV DNA load and kshv-miR-K12-1-5p level in plasma from 696 pati...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2023-06-01
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| Series: | Signal Transduction and Targeted Therapy |
| Online Access: | https://doi.org/10.1038/s41392-023-01434-3 |
| _version_ | 1797806521712640000 |
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| author | Yanru Zhao Huaping Li Hengzhi Du Zhongwei Yin Mengying He Jiahui Fan Xiang Nie Yang Sun Huiying Hou Beibei Dai Xudong Zhang Yuanyuan Cai Kunying Jin Nan Ding Zheng Wen Jiang Chang Chen Chen Dao Wen Wang |
| author_facet | Yanru Zhao Huaping Li Hengzhi Du Zhongwei Yin Mengying He Jiahui Fan Xiang Nie Yang Sun Huiying Hou Beibei Dai Xudong Zhang Yuanyuan Cai Kunying Jin Nan Ding Zheng Wen Jiang Chang Chen Chen Dao Wen Wang |
| author_sort | Yanru Zhao |
| collection | DOAJ |
| description | Abstract Dilated cardiomyopathy (DCM) is the leading cause of heart transplantation. By microRNA (miRNA) array, a Kaposi’s sarcoma-associated herpes virus (KSHV)-encoded miRNA, kshv-miR-K12-1-5p, was detected in patients with DCM. The KSHV DNA load and kshv-miR-K12-1-5p level in plasma from 696 patients with DCM were measured and these patients were followed-up. Increased KSHV seropositivity and quantitative titers were found in the patients with DCM compared with the non-DCM group (22.0% versus 9.1%, p < 0.05; 168 versus 14 copies/mL plasma, p < 0.05). The risk of the individual end point of death from cardiovascular causes or heart transplantation was increased among DCM patients with the KSHV DNA seropositivity during follow-up (adjusted hazard ratio 1.38, 95% confidence interval 1.01–1.90; p < 0.05). In heart tissues, the KSHV DNA load was also increased in the heart from patients with DCM in comparison with healthy donors (1016 versus 29 copies/105 cells, p < 0.05). The KSHV and kshv-miR-K12-1-5p in DCM hearts were detected using immunofluorescence and fluorescence staining in situ hybridization. KSHV itself was exclusively detectable in CD31-positive endothelium, while kshv-miR-K12-1-5p could be detected in both endothelium and cardiomyocytes. Moreover, kshv-miR-K12-1-5p released by KSHV-infected cardiac endothelium could disrupt the type I interferon signaling pathway in cardiomyocytes. Two models of kshv-miR-K12-1-5p overexpression (agomiR and recombinant adeno-associated virus) were used to explore the roles of KSHV-encoded miRNA in vivo. The kshv-miR-K12-1-5p aggravated known cardiotropic viruses-induced cardiac dysfunction and inflammatory infiltration. In conclusion, KSHV infection was a risk factor for DCM, providing developmental insights of DCM involving virus and its miRNA ( https://clinicaltrials.gov . Unique identifier: NCT03461107). |
| first_indexed | 2024-03-13T06:08:36Z |
| format | Article |
| id | doaj.art-8df8ab8c1bcc4beaa70f1b60c836f749 |
| institution | Directory Open Access Journal |
| issn | 2059-3635 |
| language | English |
| last_indexed | 2024-03-13T06:08:36Z |
| publishDate | 2023-06-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Signal Transduction and Targeted Therapy |
| spelling | doaj.art-8df8ab8c1bcc4beaa70f1b60c836f7492023-06-11T11:26:34ZengNature Publishing GroupSignal Transduction and Targeted Therapy2059-36352023-06-018111210.1038/s41392-023-01434-3A Kaposi’s sarcoma-associated herpes virus-encoded microRNA contributes to dilated cardiomyopathyYanru Zhao0Huaping Li1Hengzhi Du2Zhongwei Yin3Mengying He4Jiahui Fan5Xiang Nie6Yang Sun7Huiying Hou8Beibei Dai9Xudong Zhang10Yuanyuan Cai11Kunying Jin12Nan Ding13Zheng Wen14Jiang Chang15Chen Chen16Dao Wen Wang17Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDivision of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDivision of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDivision of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDivision of Cardiology, Department of Internal Medicine, Hubei Provincial Renmin HospitalDivision of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDivision of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDivision of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDivision of Cardiology, Department of Internal Medicine, The First People’s Hospital of AnqingDivision of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDivision of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDivision of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDivision of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDivision of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDivision of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Epidemiology and Biostatistics, Key Laboratory for Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and TechnologyDivision of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDivision of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyAbstract Dilated cardiomyopathy (DCM) is the leading cause of heart transplantation. By microRNA (miRNA) array, a Kaposi’s sarcoma-associated herpes virus (KSHV)-encoded miRNA, kshv-miR-K12-1-5p, was detected in patients with DCM. The KSHV DNA load and kshv-miR-K12-1-5p level in plasma from 696 patients with DCM were measured and these patients were followed-up. Increased KSHV seropositivity and quantitative titers were found in the patients with DCM compared with the non-DCM group (22.0% versus 9.1%, p < 0.05; 168 versus 14 copies/mL plasma, p < 0.05). The risk of the individual end point of death from cardiovascular causes or heart transplantation was increased among DCM patients with the KSHV DNA seropositivity during follow-up (adjusted hazard ratio 1.38, 95% confidence interval 1.01–1.90; p < 0.05). In heart tissues, the KSHV DNA load was also increased in the heart from patients with DCM in comparison with healthy donors (1016 versus 29 copies/105 cells, p < 0.05). The KSHV and kshv-miR-K12-1-5p in DCM hearts were detected using immunofluorescence and fluorescence staining in situ hybridization. KSHV itself was exclusively detectable in CD31-positive endothelium, while kshv-miR-K12-1-5p could be detected in both endothelium and cardiomyocytes. Moreover, kshv-miR-K12-1-5p released by KSHV-infected cardiac endothelium could disrupt the type I interferon signaling pathway in cardiomyocytes. Two models of kshv-miR-K12-1-5p overexpression (agomiR and recombinant adeno-associated virus) were used to explore the roles of KSHV-encoded miRNA in vivo. The kshv-miR-K12-1-5p aggravated known cardiotropic viruses-induced cardiac dysfunction and inflammatory infiltration. In conclusion, KSHV infection was a risk factor for DCM, providing developmental insights of DCM involving virus and its miRNA ( https://clinicaltrials.gov . Unique identifier: NCT03461107).https://doi.org/10.1038/s41392-023-01434-3 |
| spellingShingle | Yanru Zhao Huaping Li Hengzhi Du Zhongwei Yin Mengying He Jiahui Fan Xiang Nie Yang Sun Huiying Hou Beibei Dai Xudong Zhang Yuanyuan Cai Kunying Jin Nan Ding Zheng Wen Jiang Chang Chen Chen Dao Wen Wang A Kaposi’s sarcoma-associated herpes virus-encoded microRNA contributes to dilated cardiomyopathy Signal Transduction and Targeted Therapy |
| title | A Kaposi’s sarcoma-associated herpes virus-encoded microRNA contributes to dilated cardiomyopathy |
| title_full | A Kaposi’s sarcoma-associated herpes virus-encoded microRNA contributes to dilated cardiomyopathy |
| title_fullStr | A Kaposi’s sarcoma-associated herpes virus-encoded microRNA contributes to dilated cardiomyopathy |
| title_full_unstemmed | A Kaposi’s sarcoma-associated herpes virus-encoded microRNA contributes to dilated cardiomyopathy |
| title_short | A Kaposi’s sarcoma-associated herpes virus-encoded microRNA contributes to dilated cardiomyopathy |
| title_sort | kaposi s sarcoma associated herpes virus encoded microrna contributes to dilated cardiomyopathy |
| url | https://doi.org/10.1038/s41392-023-01434-3 |
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