The Role of Cathepsin Proteases in Reovirus Pathogenesis

Abstract

The cathepsin family of endosomal proteases is required for proteolytic processing of several viruses during entry into host cells. Mammalian reoviruses utilize cathepsins B, L, and S for disassembly of the virus outer capsid and activation of the membrane-penetration machinery. Studies using mice deficient for cathepsin B, L, or S revealed that these enzymes influence reovirus pathogenesis. Furthermore, pharmacologic modulation of cathepsin activity attenuates reovirus disease. These findings have broad implications for the role of cathepsin proteases in viral infections and suggest that cathepsin inhibitors should be developed as therapeutics.