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Journal of Virology, August 2001, p. 7429-7434, Vol. 75, No. 16
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.16.7429-7434.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Reovirus-Induced sigma 1s-Dependent G2/M Phase Cell Cycle Arrest Is Associated with Inhibition of p34cdc2

George J. Poggioli,1 Terence S. Dermody,2,3,4 and Kenneth L. Tyler1,5,6,7,8,*

Departments of Neurology,5 Medicine,6 Microbiology,1 and Immunology,7 University of Colorado Health Sciences Center, and Neurology Service, Denver Veterans Affairs Medical Center,8 Denver, Colorado 80220, and Departments of Pediatrics2 and Microbiology and Immunology3 and Elizabeth B. Lamb Center for Pediatric Research,4 Vanderbilt University School of Medicine, Nashville, Tennessee 37232

Received 28 February 2001/Accepted 23 May 2001

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 sigma 1s 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 sigma 1s protein is necessary and sufficient for inhibitory phosphorylation of p34cdc2, since a viral mutant lacking sigma 1s fails to hyperphosphorylate p34cdc2 and inducible expression of sigma 1s is sufficient for p34cdc2 hyperphosphorylation. These studies establish a mechanism by which reovirus can perturb cell cycle regulation.

* Corresponding author. Mailing address: Department of Neurology (B-182), University of Colorado Health Sciences Center, 4200 E. 9th Ave., Denver, CO 80262. Phone: (303) 393-2874. Fax: (303) 393-4686. E-mail: Ken.Tyler{at}UCHSC.edu.

Journal of Virology, August 2001, p. 7429-7434, Vol. 75, No. 16
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.16.7429-7434.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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