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

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.