Related Experiment Video
Updated: May 15, 2025
Viral Transgene Expression in Rodent Hearts and the Assessment of Cardiac Arrhythmia Risk
Published on: July 27, 2022
Targeting Viperin prevents coxsackievirus B3-induced acute heart failure
Yukang Yuan1,2,3,4, Liping Qian1,2, Ying Miao1,2,4
1The First Affiliated Hospital of Soochow University, Institutes of Biology and Medical Sciences, Suzhou Medical College, Soochow University, Suzhou, Jiangsu, China.
Insights
Viperin deficiency protects against Coxsackievirus B3-induced acute heart failure (AHF) by preventing cardiac electrical dysfunction. An interfering peptide targeting Viperin shows potential for treating AHF.
Area of Science:
- Cardiology
- Virology
- Molecular Biology
Background:
- Coxsackievirus B3 (CVB3) causes acute heart failure (AHF), a major cause of death.
- Molecular mechanisms linking CVB3 to AHF are poorly understood, hindering targeted therapies.
Purpose of the Study:
- To elucidate the molecular events connecting CVB3 infection to AHF.
- To identify potential therapeutic targets for CVB3-induced AHF.
Main Methods:
- Investigated the role of Viperin in CVB3-induced AHF using mouse models.
- Analyzed molecular pathways involving Viperin, STAT1, SGK1-KCNQ1 signaling, and CVB3 3C protease.
- Developed and tested an interfering peptide (VS-IP1).
Main Results:
- Viperin deficiency protected mice from CVB3-induced AHF.
- Cardiac-specific Viperin expression induced cardiac dysfunction.
- CVB3 3C protease lowers UBE4A to increase Viperin, which reduces STAT1, activating SGK1-KCNQ1 signaling and causing cardiac electrical dysfunction.
- VS-IP1 peptide blocked Viperin-mediated STAT1 degradation and prevented AHF.
Conclusions:
- Established a signaling link between CVB3 and cardiac electrical dysfunction via Viperin.
- Viperin is a key mediator of CVB3-induced AHF.
- Interfering peptides targeting Viperin offer a potential therapeutic strategy for AHF.
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.
Related Concept Videos
01:22Heart Failure Drugs: β-Blockers
01:26Heart Failure Drugs: Inhibitors of Renin-Angiotensin System
01:26Heart Failure Drugs: Inotropic Agents
01:22Heart Failure Drugs: Diuretics