Targeting Viperin prevents coxsackievirus B3-induced acute heart failure

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.

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Publication Details

Journal
Cell Discovery
Published
2025-04-08
DOI
https://doi.org/10.1038/s41421-025-00778-0
Citations
2
Primary Topic
Viral Infections and Immunology Research
Type
article
Field-Weighted Citation Impact
2.78

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article

Targeting Viperin prevents coxsackievirus B3-induced acute heart failure

Yukang Yuan, Meng Li, Ruizhen Chen, Ting Cao et al.
2 citations
Cell Discovery
Viral Infections and Immunology Research
2.78
article

Targeting Viperin prevents coxsackievirus B3-induced acute heart failure

Yukang Yuan, Meng Li, Ruizhen Chen, Ting Cao, Yibo Zuo, Liping Qian, Sidong Xiong, Zhijin Zheng, Qian Zhao, Tianqing Peng, Hui Zheng, Renxia Zhang, Qiuyu Wu, Tengfei Ren, Caixia Qiao, Ying Miao, Tingting Zhang, Yong Yu, Qian Du, Qun Cui, Wei Xu, Y. Eugene Chinn
article en
2 citations

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.

Cell DiscoveryVol. 11(1)
Western University (CA), Lawson Health Research Institute (CA), University of Electronic Science and Technology of China (CN), Sun Yat-sen University (CN), Nantong University (CN), Fudan University (CN), London Health Sciences Centre (CA), Soochow University (CN), Zhongshan Hospital (CN), The First Affiliated Hospital, Sun Yat-sen University (CN), First Affiliated Hospital of Soochow University (CN)
Yale University, University of Pennsylvania, National Natural Science Foundation of China, Chinese Academy of Sciences, China Pharmaceutical University, China Postdoctoral Science Foundation, Fudan University, Soochow University, Priority Academic Program Development of Jiangsu Higher Education Institutions, Fujian Medical University, Institute of Zoology, Chinese Academy of Sciences
Good health and well-being
Openalex Percentile: Top 10%
Viral Infections and Immunology Research
2.78
DOIOpen Access PDFOpenAlex
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