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Journal of Virology, October 2000, p. 9562-9570, Vol. 74, No. 20
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Reovirus-Induced G2/M Cell Cycle Arrest Requires sigma 1s and Occurs in the Absence of Apoptosis

George J. Poggioli,1 Christopher Keefer,2 Jodi L. Connolly,3,4 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 1 May 2000/Accepted 18 July 2000

Serotype-specific differences in the capacity of reovirus strains to inhibit proliferation of murine L929 cells correlate with the capacity to induce apoptosis. The prototype serotype 3 reovirus strains Abney (T3A) and Dearing (T3D) inhibit cellular proliferation and induce apoptosis to a greater extent than the prototype serotype 1 reovirus strain Lang (T1L). We now show that reovirus-induced inhibition of cellular proliferation results from a G2/M cell cycle arrest. Using T1L × T3D reassortant viruses, we found that strain-specific differences in the capacity to induce G2/M arrest, like the differences in the capacity to induce apoptosis, are determined by the viral S1 gene. The S1 gene is bicistronic, encoding the viral attachment protein sigma 1 and the nonstructural protein sigma 1s. A sigma 1s-deficient reovirus strain, T3C84-MA, fails to induce G2/M arrest, yet retains the capacity to induce apoptosis, indicating that sigma 1s is required for reovirus-induced G2/M arrest. Expression of sigma 1s in C127 cells increases the percentage of cells in the G2/M phase of the cell cycle, supporting a role for this protein in reovirus-induced G2/M arrest. Inhibition of reovirus-induced apoptosis failed to prevent virus-induced G2/M arrest, indicating that G2/M arrest is not the result of apoptosis related DNA damage and suggests that these two processes occur through distinct pathways.


* 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, October 2000, p. 9562-9570, Vol. 74, No. 20
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.



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