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A Kaposi’s sarcoma-associated herpes virus-encoded microRNA contributes to dilated cardiomyopathy
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...
Autores principales: | , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10250357/ https://www.ncbi.nlm.nih.gov/pubmed/37291118 http://dx.doi.org/10.1038/s41392-023-01434-3 |
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author | Zhao, Yanru Li, Huaping Du, Hengzhi Yin, Zhongwei He, Mengying Fan, Jiahui Nie, Xiang Sun, Yang Hou, Huiying Dai, Beibei Zhang, Xudong Cai, Yuanyuan Jin, Kunying Ding, Nan Wen, Zheng Chang, Jiang Chen, Chen Wang, Dao Wen |
author_facet | Zhao, Yanru Li, Huaping Du, Hengzhi Yin, Zhongwei He, Mengying Fan, Jiahui Nie, Xiang Sun, Yang Hou, Huiying Dai, Beibei Zhang, Xudong Cai, Yuanyuan Jin, Kunying Ding, Nan Wen, Zheng Chang, Jiang Chen, Chen Wang, Dao Wen |
author_sort | Zhao, Yanru |
collection | PubMed |
description | 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/10(5) 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). |
format | Online Article Text |
id | pubmed-10250357 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-102503572023-06-10 A Kaposi’s sarcoma-associated herpes virus-encoded microRNA contributes to dilated cardiomyopathy Zhao, Yanru Li, Huaping Du, Hengzhi Yin, Zhongwei He, Mengying Fan, Jiahui Nie, Xiang Sun, Yang Hou, Huiying Dai, Beibei Zhang, Xudong Cai, Yuanyuan Jin, Kunying Ding, Nan Wen, Zheng Chang, Jiang Chen, Chen Wang, Dao Wen Signal Transduct Target Ther Article 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/10(5) 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). Nature Publishing Group UK 2023-06-09 /pmc/articles/PMC10250357/ /pubmed/37291118 http://dx.doi.org/10.1038/s41392-023-01434-3 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Zhao, Yanru Li, Huaping Du, Hengzhi Yin, Zhongwei He, Mengying Fan, Jiahui Nie, Xiang Sun, Yang Hou, Huiying Dai, Beibei Zhang, Xudong Cai, Yuanyuan Jin, Kunying Ding, Nan Wen, Zheng Chang, Jiang Chen, Chen Wang, Dao Wen A Kaposi’s sarcoma-associated herpes virus-encoded microRNA contributes to dilated cardiomyopathy |
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 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10250357/ https://www.ncbi.nlm.nih.gov/pubmed/37291118 http://dx.doi.org/10.1038/s41392-023-01434-3 |
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