Reovirus-Induced ς1s-Dependent G 2 /M Phase Cell Cycle Arrest Is Associated with Inhibition of p34 cdc2

Abstract

ABSTRACT Serotype 3 reoviruses inhibit cellular proliferation by inducing a G 2 /M phase cell cycle arrest. Reovirus-induced G 2 /M phase arrest requires the viral S1 gene-encoded ς1s nonstructural protein. The G 2 -to-M transition represents a cell cycle checkpoint that is regulated by the kinase p34 cdc2 . We now report that infection with serotype 3 reovirus strain Abney, but not serotype 1 reovirus strain Lang, is associated with inhibition and hyperphosphorylation of p34 cdc2 . The ς1s protein is necessary and sufficient for inhibitory phosphorylation of p34 cdc2 , since a viral mutant lacking ς1s fails to hyperphosphorylate p34 cdc2 and inducible expression of ς1s is sufficient for p34 cdc2 hyperphosphorylation. These studies establish a mechanism by which reovirus can perturb cell cycle regulation.