Targeting Viperin prevents coxsackievirus B3-induced acute heart failure
Abstract Coxsackievirus B3 (CVB3)-induced acute heart failure (AHF) is a common cause of cardiogenic death in young- and middle-aged people. However, the key molecular events linking CVB3 to AHF remain largely unknown, resulting in a lack of targeted therapy strategies thus far. Here, we unexpectedl...
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2025-04-01
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| Series: | Cell Discovery |
| Online Access: | https://doi.org/10.1038/s41421-025-00778-0 |
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| author | Yukang Yuan Liping Qian Ying Miao Qun Cui Ting Cao Yong Yu Tingting Zhang Qian Zhao Renxia Zhang Tengfei Ren Yibo Zuo Qian Du Caixia Qiao Qiuyu Wu Zhijin Zheng Minqi Li Y. Eugene Chinn Wei Xu Tianqing Peng Ruizhen Chen Sidong Xiong Hui Zheng |
| author_facet | Yukang Yuan Liping Qian Ying Miao Qun Cui Ting Cao Yong Yu Tingting Zhang Qian Zhao Renxia Zhang Tengfei Ren Yibo Zuo Qian Du Caixia Qiao Qiuyu Wu Zhijin Zheng Minqi Li Y. Eugene Chinn Wei Xu Tianqing Peng Ruizhen Chen Sidong Xiong Hui Zheng |
| author_sort | Yukang Yuan |
| collection | DOAJ |
| description | Abstract Coxsackievirus B3 (CVB3)-induced acute heart failure (AHF) is a common cause of cardiogenic death in young- and middle-aged people. However, the key molecular events linking CVB3 to AHF remain largely unknown, resulting in a lack of targeted therapy strategies thus far. Here, we unexpectedly found that Viperin deficiency does not promote CVB3 infection but protects mice from CVB3-induced AHF. Importantly, cardiac-specific expression of Viperin can induce cardiac dysfunction. Mechanistically, CVB3-encoded 3C protease rescues Viperin protein expression in cardiomyocytes by lowering UBE4A. Viperin in turn interacts with and reduces STAT1 to activate SGK1-KCNQ1 signaling, and eventually leads to cardiac electrical dysfunction and subsequent AHF. Furthermore, we designed an interfering peptide VS-IP1, which blocked Viperin-mediated STAT1 degradation and therefore prevented CVB3-induced AHF. This study established the first signaling link between CVB3 and cardiac electrical dysfunction, and revealed the potential of interfering peptides targeting Viperin for the treatment of CVB3-induced AHF. |
| format | Article |
| id | doaj-art-0417caae2f66473c8dbf09a4c7666a36 |
| institution | OA Journals |
| issn | 2056-5968 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Discovery |
| spelling | doaj-art-0417caae2f66473c8dbf09a4c7666a362025-08-20T02:16:06ZengNature Publishing GroupCell Discovery2056-59682025-04-0111111510.1038/s41421-025-00778-0Targeting Viperin prevents coxsackievirus B3-induced acute heart failureYukang Yuan0Liping Qian1Ying Miao2Qun Cui3Ting Cao4Yong Yu5Tingting Zhang6Qian Zhao7Renxia Zhang8Tengfei Ren9Yibo Zuo10Qian Du11Caixia Qiao12Qiuyu Wu13Zhijin Zheng14Minqi Li15Y. Eugene Chinn16Wei Xu17Tianqing Peng18Ruizhen Chen19Sidong Xiong20Hui Zheng21The First Affiliated Hospital of Soochow University, Institutes of Biology and Medical Sciences, Suzhou Medical College, Soochow UniversityThe First Affiliated Hospital of Soochow University, Institutes of Biology and Medical Sciences, Suzhou Medical College, Soochow UniversityThe First Affiliated Hospital of Soochow University, Institutes of Biology and Medical Sciences, Suzhou Medical College, Soochow UniversityThe First Affiliated Hospital of Soochow University, Institutes of Biology and Medical Sciences, Suzhou Medical College, Soochow UniversityInstitute for Cardiovascular Science, Collaborative Innovation Center of Hematology, Soochow UniversityDepartment of Cardiology, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan UniversityThe First Affiliated Hospital of Soochow University, Institutes of Biology and Medical Sciences, Suzhou Medical College, Soochow UniversityThe First Affiliated Hospital of Soochow University, Institutes of Biology and Medical Sciences, Suzhou Medical College, Soochow UniversityThe First Affiliated Hospital of Soochow University, Institutes of Biology and Medical Sciences, Suzhou Medical College, Soochow UniversityThe First Affiliated Hospital of Soochow University, Institutes of Biology and Medical Sciences, Suzhou Medical College, Soochow UniversityThe First Affiliated Hospital of Soochow University, Institutes of Biology and Medical Sciences, Suzhou Medical College, Soochow UniversityThe First Affiliated Hospital of Soochow University, Institutes of Biology and Medical Sciences, Suzhou Medical College, Soochow UniversityThe First Affiliated Hospital of Soochow University, Institutes of Biology and Medical Sciences, Suzhou Medical College, Soochow UniversityThe First Affiliated Hospital of Soochow University, Institutes of Biology and Medical Sciences, Suzhou Medical College, Soochow UniversityThe First Affiliated Hospital of Soochow University, Institutes of Biology and Medical Sciences, Suzhou Medical College, Soochow UniversityMedical College of Nantong UniversityInternational Institute of Infection and Immunity, Institutes of Biology and Medical Sciences, Soochow UniversityInternational Institute of Infection and Immunity, Institutes of Biology and Medical Sciences, Soochow UniversityLawson Health Research Institute, London Health Sciences CentreDepartment of Cardiology, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan UniversityInternational Institute of Infection and Immunity, Institutes of Biology and Medical Sciences, Soochow UniversityThe First Affiliated Hospital of Soochow University, Institutes of Biology and Medical Sciences, Suzhou Medical College, Soochow UniversityAbstract Coxsackievirus B3 (CVB3)-induced acute heart failure (AHF) is a common cause of cardiogenic death in young- and middle-aged people. However, the key molecular events linking CVB3 to AHF remain largely unknown, resulting in a lack of targeted therapy strategies thus far. Here, we unexpectedly found that Viperin deficiency does not promote CVB3 infection but protects mice from CVB3-induced AHF. Importantly, cardiac-specific expression of Viperin can induce cardiac dysfunction. Mechanistically, CVB3-encoded 3C protease rescues Viperin protein expression in cardiomyocytes by lowering UBE4A. Viperin in turn interacts with and reduces STAT1 to activate SGK1-KCNQ1 signaling, and eventually leads to cardiac electrical dysfunction and subsequent AHF. Furthermore, we designed an interfering peptide VS-IP1, which blocked Viperin-mediated STAT1 degradation and therefore prevented CVB3-induced AHF. This study established the first signaling link between CVB3 and cardiac electrical dysfunction, and revealed the potential of interfering peptides targeting Viperin for the treatment of CVB3-induced AHF.https://doi.org/10.1038/s41421-025-00778-0 |
| spellingShingle | Yukang Yuan Liping Qian Ying Miao Qun Cui Ting Cao Yong Yu Tingting Zhang Qian Zhao Renxia Zhang Tengfei Ren Yibo Zuo Qian Du Caixia Qiao Qiuyu Wu Zhijin Zheng Minqi Li Y. Eugene Chinn Wei Xu Tianqing Peng Ruizhen Chen Sidong Xiong Hui Zheng Targeting Viperin prevents coxsackievirus B3-induced acute heart failure Cell Discovery |
| title | Targeting Viperin prevents coxsackievirus B3-induced acute heart failure |
| title_full | Targeting Viperin prevents coxsackievirus B3-induced acute heart failure |
| title_fullStr | Targeting Viperin prevents coxsackievirus B3-induced acute heart failure |
| title_full_unstemmed | Targeting Viperin prevents coxsackievirus B3-induced acute heart failure |
| title_short | Targeting Viperin prevents coxsackievirus B3-induced acute heart failure |
| title_sort | targeting viperin prevents coxsackievirus b3 induced acute heart failure |
| url | https://doi.org/10.1038/s41421-025-00778-0 |
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