Coxsackievirus B3 Employs Viperin Protein Revived by the 3C Protease to Induce Acute Heart Failure via SGK1-KCNQ1 Signaling

Published: 11 July 2023| Version 1 | DOI: 10.17632/zny9vb387g.1
yukang yuan


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 so far. Here, we unexpectedly found that deficiency of Viperin does not promote CVB3 infection but protects mice from CVB3-induced AHF. Importantly, cardiac-specific expression of Viperin can induce cardiac dysfunction. Mechanistically, CVB3-3C protease rescues Viperin protein expression in cardiomyocytes by cleaving UBE4A. Viperin in turn recruits and reduces STAT1 to activate SGK1-KCNQ1 signaling, which leads to cardiac electrical dysfunction and subsequent AHF. Furthermore, we designed an interfering peptide VS-IP1, which blocked Viperin-mediated STAT1 degradation and restricted CVB3-induced AHF. This study established the first signaling linker between CVB3 and AHF-associated cardiac electrical dysfunction, and reveals the potential of interfering peptides targeting Viperin for the treatment of CVB3-induced AHF.



Acute Heart Failure