In search of cathepsins: how reovirus enters host cells

Abstract

Encapsidated viruses bind cell surface receptors and enter through receptor-mediated endocytosis. The next step in infection requires uncoating of the virion. In this inaugural BIT, the role of proteases of the Cathepsin family, which are found endosomes, are critical for viral replication.

FIG. 1.

Model of reovirus cell entry. After attachment to cell-surface sialic acid and junctional adhesion molecule A (JAM-A), reovirus enters cells by receptor-mediated endocytosis (1) in a β1 integrin-dependent manner. Activation of Src kinase (2) at the site of entry targets reovirus to early endosomes (3), inhabited by inactive cathepsin proteases (cathepsin zymogens). In a productive infection, viral particles remain associated with JAM-A, and perhaps β1 integrin, and traverse to late endosomes where active cathepsin proteases mediate disassembly of viral particles, resulting in the release of the transcriptionally active viral core into the cytoplasm (4). In a nonproductive infection (5), viral particles traffic to fast and slow recycling compartments. The fate of viral particles within recycling endosomes is not known, but it is possible that these particles are redirected to the cell surface where they can reinitiate the entry process or disengage from receptors.