This work will be interpreted in the context of ongoing structural studies of s 1 with the goal of determining how s 1 structure relates to its function in receptor binding. Reovirus enters cells by receptor-mediated endocytosis. We have isolated mutant viruses altered in their requirement for acid-dependent proteolysis and mutant cells that do not support proteolytic disassembly of reovirus virions. Biochemical, genetic and structural studies using these mutant viruses and cells are ongoing to define mechanisms of reovirus entry. This research will reveal fundamental mechanisms by which viral and cellular factors cooperate to facilitate viral entry and illuminate new targets for therapy against viruses that use the endocytic pathway to enter cells.
Reovirus induces apoptosis in both cultured cells and in the murine central nervous system.
Our studies indicate that apoptosis is triggered by a signal-transduction cascade initiated by reovirus attachment to its cellular receptor. Experiments are in progress to identify components of the cell-signaling apparatus required for apoptosis induction by reovirus and to determine the relationship between apoptosis and reovirus virulence. Identification of carbohydrate-binding domains in the attachment proteins of type 1 and type 3 reoviruses. B. J. Virol. Mutant cells selected during persistent reovirus infection do not express mature cathepsin L and do not support reovirus disassembly.