Cathepsin B aggravates coxsackievirus B3-induced myocarditis through activating the inflammasome and promoting pyroptosis

Author summary Severe VMC could lead to sudden cardiac death especially in youths, and is also the most common cause of secondary dilated cardiomyopathy. However, we still lack effective and specific clinical treatments currently. Therefore, further exploration of the pathogenesis and new therapeutic targets are urgently needed. Our results implied that CatB, a cysteine protease mainly located in the lysosome, is activated in the hearts of mice with VMC induced by intraperitoneal injection of CVB3. Genetic deletion of CatB significantly improves survival, attenuates cardiac inflammation, decreases serum cardiac troponin I levels and alleviates cardiac dysfunction, without altering virus titers in hearts. However, ablation of its main endogenous inhibitor, cystatin C, distinctly exaggerates the disease severity. Mechanistically, we found that CatB influences VMC probably by activating the NLRP3 inflammasome and promoting caspase-1-induced pyroptosis. This may provide a potential new therapeutic strategy for VMC.See it on Scoop.it, via Viruses, Immunology & Bioinformatics from Virology.uvic.ca
Cathepsin B aggravates coxsackievirus B3-induced myocarditis through activating the inflammasome and promoting pyroptosis
Source: Viral Bioinformatics