Cathepsin B hyperactivation facilitates exosome release of CVB3 particles and exacerbation of acute pancreatitis by impairing lysosomal integrity and acidification

This study uncovers a critical role of lysosome cathepsin B (CTSB) in exacerbating viral acute pancreatitis (AP). CVB3 infection of acinar cells induces lysosomal membrane permeability and CTSB cytosolic translocation. Hyperactivated CTSB increases viral infections by decreasing lysosomes, exacerbating LMP, and enhancing exosomal release of virions. Pharmaceutical inhibition of CTSB protects mice against viral dissemination and AP pathology, suggesting that CTSB and exosome are potential therapeutic targets for viral AP.