Reovirus-Induced G 2 /M Cell Cycle Arrest Requires ς1s and Occurs in the Absence of Apoptosis

Author:

Poggioli George J.1,Keefer Christopher2,Connolly Jodi L.34,Dermody Terence S.234,Tyler Kenneth L.56178

Affiliation:

1. Microbiology,1 and

2. Departments of Pediatrics2and

3. Microbiology and Immunology3 and

4. Elizabeth B. Lamb Center for Pediatric Research,4 Vanderbilt University School of Medicine, Nashville, Tennessee 37232

5. Departments of Neurology,5

6. Medicine,6

7. Immunology,7 University of Colorado Health Sciences Center, and

8. Neurology Service, Denver Veterans Affairs Medical Center,8 Denver, Colorado 80220, and

Abstract

ABSTRACT 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 G 2 /M cell cycle arrest. Using T1L × T3D reassortant viruses, we found that strain-specific differences in the capacity to induce G 2 /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 ς1 and the nonstructural protein ς1s. A ς1s-deficient reovirus strain, T3C84-MA, fails to induce G 2 /M arrest, yet retains the capacity to induce apoptosis, indicating that ς1s is required for reovirus-induced G 2 /M arrest. Expression of ς1s in C127 cells increases the percentage of cells in the G 2 /M phase of the cell cycle, supporting a role for this protein in reovirus-induced G 2 /M arrest. Inhibition of reovirus-induced apoptosis failed to prevent virus-induced G 2 /M arrest, indicating that G 2 /M arrest is not the result of apoptosis related DNA damage and suggests that these two processes occur through distinct pathways.

Publisher

American Society for Microbiology

Subject

Virology,Insect Science,Immunology,Microbiology

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