Reovirus-Induced ς1s-Dependent G2/M Phase Cell Cycle Arrest Is Associated with Inhibition of p34cdc2 |
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Authors: | George J Poggioli Terence S Dermody and Kenneth L Tyler |
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Institution: | Department of Microbiology, and Neurology Service, Denver Veterans Affairs Medical Center, Denver, Colorado 80220, USA. |
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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 sigma1s 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 sigma1s protein is necessary and sufficient for inhibitory phosphorylation of p34(cdc2), since a viral mutant lacking sigma1s fails to hyperphosphorylate p34(cdc2) and inducible expression of sigma1s is sufficient for p34(cdc2) hyperphosphorylation. These studies establish a mechanism by which reovirus can perturb cell cycle regulation. |
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