Reovirus-induced σ1s-dependent G2/M phase cell cycle arrest is associated with inhibition of p34cdc2

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 sigma 1s nonstructural protein. The G(2)-to-M transition represents a cell cycle checkpoint that is regulated by the kinase p34(cd2). We now report that infection with serotype 3 reovirus strain Abney, but not serotype I reovirus strain Lang, is associated with inhibition and hyperphosphorylation of p34(cdc2). The als protein is necessary and sufficient for inhibitory phosphorylation of p34(cdc2), since a viral mutant lacking als fails to hyperphosphorylate p34(cdc2) and inducible expression of als is sufficient for p34(cdc2) hyperphosphorylation. These studies establish a mechanism by which reovirus can perturb cell cycle regulation.