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

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Abstract
Serotype 3 reoviruses inhibit cellular proliferation by inducing a G2/M phase cell cycle arrest. Reovirus-induced G2/M phase arrest requires the viral S1 gene-encoded ς1s nonstructural protein. The G2-to-M transition represents a cell cycle checkpoint that is regulated by the kinase p34cdc2. 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 p34cdc2. The ς1s protein is necessary and sufficient for inhibitory phosphorylation of p34cdc2, since a viral mutant lacking ς1s fails to hyperphosphorylate p34cdc2 and inducible expression of ς1s is sufficient for p34cdc2hyperphosphorylation. These studies establish a mechanism by which reovirus can perturb cell cycle regulation.