Ctsw, also known as cathepsin W, is a cysteine protease. It is involved in multiple biological processes. In the immune system, it plays a role in T-cell function, and in viral infections, it is required for influenza A virus (IAV) to escape from late endosomes [2,3]. It may also be involved in processes related to tumor-associated fibrosis and mucosal immune quiescence [1,4]. Genetic models, such as gene-knockout mouse models, are valuable for studying its functions.

In gene-function studies, knockdown of CtsW in cells leads to a decrease in IAV nucleoprotein accumulation in the nuclei of infected cells, with impaired escape of viral particles from late endosomes [2]. CtsW-deficient mice show a 25% increase in survival and a delay in mortality upon IAV infection [3]. Loss of CtsW in mice results in elevated peripheral regulatory T (pTreg) cell generation, protecting animals from intestinal inflammation. Mechanistically, CtsW inhibits IL-2R signaling in pTreg cells [4].

In conclusion, CtsW is an important cysteine protease. Its functions in viral entry and immune-cell regulation, as revealed through gene-knockout mouse models, have implications for antiviral therapies and understanding mucosal immune tolerance. These model-based studies contribute to our knowledge of how CtsW is involved in influenza A virus infection and mucosal immune-related disease conditions.