Targeting Viperin prevents coxsackievirus B3-induced acute heart failure

作者：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, Meng Li, Y. Eugene Chinn, Wei Xu, Tianqing Peng, Ruizhen Chen, Sidong Xiong, Hui Zheng · 发表于：Cell Discovery · 年份：2025 · DOI：10.1038/s41421-025-00778-0 · 被引用次数：4 · 研究领域：Viral Infections and Immunology Research、RNA and protein synthesis mechanisms、interferon and immune responses

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.