Cathepsins encompass a family of lysosomal proteases that mediate protein degradation and turnover. Although mainly localized in the endolysosomal compartment, cathepsins are also found in the cytoplasm, nucleus, and extracellular space, where they are involved in cell signaling, extracellular matrix assembly/disassembly, and protein processing and trafficking through the plasma and nuclear membrane and between intracellular organelles. Ubiquitously expressed in the body, cathepsins play regulatory roles in a wide range of physiological processes including coagulation, hormone secretion, immune responses, and others. A dysregulation of cathepsin expression and/or activity has been associated with many human diseases, including cancer, diabetes, obesity, cardiovascular and inflammatory diseases, kidney dysfunctions, and neurodegenerative disorders, as well as infectious diseases. In viral infections, cathepsins may promote (1) activation of the viral attachment glycoproteins and entry of the virus into target cells; (2) antigen processing and presentation, enabling the virus to replicate in infected cells; (3) up-regulation and processing of heparanase that facilitates the release of viral progeny and the spread of infection; and (4) activation of cell death that may either favor viral clearance or assist viral propagation. In this review, we report the most relevant findings on the molecular mechanisms underlying cathepsin involvement in viral infection physiopathology, and we discuss the potential of cathepsin inhibitors for therapeutical applications in viral infectious diseases.

Cathepsins are protease enzymes vital for normal physiological functions, such as digestion, coagulation, hormone secretion, bone resorption, apoptosis, autophagy, and both innate and adaptive immunity. Their altered expression and/or activity is associated with various pathological conditions, including inflammatory processes. In this study, we investigated the expression levels of cathepsins in muscle specimens collected from dogs affected by inflammatory myopathy (IM) of variable severity established through histopathological analysis. Samples collected from dogs affected by IM at mild, moderate, and severe stages and from healthy (control) dogs were analyzed for the expression profile of 35 proteases using a proteome profiler array. Among the other proteases, cathepsin B was upregulated to an extent depending on disease progression. By exploring the molecular mechanisms underlying the impact of cathepsin B on the disease, we found that the upregulation of cathepsin B in diseased tissues correlates with increased TGFβ-1 expression levels and elevated phosphorylation levels of the TGFβ-1 signaling mediator SMAD2/3. These results suggest that cathepsin B might be involved in the onset and progression of fibrosis commonly occurring in IM diseased dogs. Overall, our findings reveal that modulating cathepsin B activity may hold therapeutic potential for IM.