B组柯萨奇病毒（CVB）是病毒性心肌炎及扩张型心肌病的主要病原，尚无有效治疗手段。其3C蛋白酶可特异性切割宿主蛋白，在病毒致病中发挥重要作用。维持线粒体稳态是心肌细胞发挥正常功能的关键，线粒体自噬可清除损伤或衰老的线粒体，是调控线粒体稳态的关键环节之一。我们前期研究显示CVB 3C蛋白酶有可能切割线粒体自噬关键分子Parkin，从而抑制线粒体自噬水平。据此推测CVB通过干扰线粒体自噬，破坏线粒体稳态，进而导致心肌细胞损伤。本项目将通过体内和体外实验阐明CVB干扰心肌细胞线粒体稳态的机制：①明确CVB感染抑制心肌细胞线粒体自噬；②阐明CVB抑制线粒体自噬的分子机制；③评价CVB通过抑制线粒体自噬对心肌结构功能及能量代谢的影响。本项目可能揭示CVB对宿主细胞造成损伤的新的分子机制，并为研发抗CVB药物提供新靶点。

Coxsackievirus B (CVB) is the major pathogen of human viral myocarditis and dilated cardiomyopathy. Presently, effective therapy is not available. The 3C protease of CVB, plays an essential role in virus pathogenesis, which can cleave host proteins specifically. The maintenance of mitochondrial homeostasis is essential for the myocardial function, mitophagy could eliminate the damaged or effete mitochondria, which is a vital pathway regulating mitochondrial homeostasis. Our previous study demonstrated that the 3C protease of CVB may cleave host proteins specifically, and mitophagy can be inhibited by CVB infection. Based on the above, we speculate CVB can impair cardiomyocytes through disrupting mitophagy. This study was designed to investigate the mechanism of coxsackivirus B disrupting myocardial mitophagy through in vivo and in vitro approaches: (1) To make sure that CVB infection can inhibit mitophagy in cardiac cells. (2) To elucidate the mechanism of CVB interdicting mitophagy. (3) To evaluate the changes of myocardial structure and function, and the subsequent aggravation of host damage caused by CVB through inhibiting mitophagy. This study would uncover a novel significant mechanism for the cardiac damage associated with CVB infection, which could provide a new target for drug discovery treating CVB infection.