2. Academic Validation
  3. Targeting Viperin prevents coxsackievirus B3-induced acute heart failure

Targeting Viperin prevents coxsackievirus B3-induced acute heart failure

  • Cell Discov. 2025 Apr 8;11(1):34. doi: 10.1038/s41421-025-00778-0.
Yukang Yuan # 1 2 3 4,  Liping Qian # 1 2,  Ying Miao # 1 2 4,  Qun Cui # 1 2,  Ting Cao 5,  Yong Yu 6,  Tingting Zhang 1 2 3,  Qian Zhao 1 2 3,  Renxia Zhang 1 2 3,  Tengfei Ren 1 2 3,  Yibo Zuo 1 2 3,  Qian Du 1 2 3,  Caixia Qiao 1 2 3,  Qiuyu Wu 1 2 3,  Zhijin Zheng 1 2 3,  Minqi Li 7,  Y Eugene Chinn 2 3,  Wei Xu 2 3,  Tianqing Peng 8 9,  Ruizhen Chen 10,  Sidong Xiong 11 12,  Hui Zheng 13 14 15
Affiliations

Affiliations

  • 1 The First Affiliated Hospital of Soochow University, Institutes of Biology and Medical Sciences, Suzhou Medical College, Soochow University, Suzhou, Jiangsu, China.
  • 2 International Institute of Infection and Immunity, Institutes of Biology and Medical Sciences, Soochow University, Suzhou, Jiangsu, China.
  • 3 Jiangsu Key Laboratory of Infection and Immunity, Soochow University, Suzhou, Jiangsu, China.
  • 4 Department of Laboratory Medicine, Institute of Laboratory Medicine, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, China.
  • 5 Institute for Cardiovascular Science, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, Jiangsu, China.
  • 6 Department of Cardiology, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, China.
  • 7 Medical College of Nantong University, Nantong, Jiangsu, China.
  • 8 Lawson Health Research Institute, London Health Sciences Centre, London, ON, Canada.
  • 9 Department of Medicine, Department of Pathology and Laboratory Medicine, Western University, London, ON, Canada.
  • 10 Department of Cardiology, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, China. chen.ruizhen@zs-hospital.sh.cn.
  • 11 International Institute of Infection and Immunity, Institutes of Biology and Medical Sciences, Soochow University, Suzhou, Jiangsu, China. sdxiong@suda.edu.cn.
  • 12 Jiangsu Key Laboratory of Infection and Immunity, Soochow University, Suzhou, Jiangsu, China. sdxiong@suda.edu.cn.
  • 13 The First Affiliated Hospital of Soochow University, Institutes of Biology and Medical Sciences, Suzhou Medical College, Soochow University, Suzhou, Jiangsu, China. huizheng@suda.edu.cn.
  • 14 International Institute of Infection and Immunity, Institutes of Biology and Medical Sciences, Soochow University, Suzhou, Jiangsu, China. huizheng@suda.edu.cn.
  • 15 Department of Laboratory Medicine, Institute of Laboratory Medicine, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, China. huizheng@suda.edu.cn.
  • # Contributed equally.
PMID: 40195316 DOI: 10.1038/s41421-025-00778-0
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.

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