Targeting Viperin prevents coxsackievirus B3-induced acute heart failure

Targeting Viperin prevents coxsackievirus B3-induced acute heart failure

Blog Article

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 Sewing 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 EZEKIEL BREAD LOW SODIUM the treatment of CVB3-induced AHF.