Targeting Viperin prevents coxsackievirus B3-induced acute heart failure PMID: 40195316

ADC Targets in Oncology

2026-04-10

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

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. [email protected].
11. International Institute of Infection and Immunity, Institutes of Biology and Medical Sciences, Soochow University, Suzhou, Jiangsu, China. [email protected].
12. Jiangsu Key Laboratory of Infection and Immunity, Soochow University, Suzhou, Jiangsu, China. [email protected].
13. The First Affiliated Hospital of Soochow University, Institutes of Biology and Medical Sciences, Suzhou Medical College, Soochow University, Suzhou, Jiangsu, China. [email protected].
14. International Institute of Infection and Immunity, Institutes of Biology and Medical Sciences, Soochow University, Suzhou, Jiangsu, China. [email protected].
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. [email protected].
# Contributed equally.

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.