Reovirus-induced sigma1s-dependent G(2)/M phase cell cycle arrest is associated with inhibition of p34(cdc2).
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.
Poggioli
G J
GJ
Department of Microbiology, and Neurology Service, Denver Veterans Affairs Medical Center, Denver, Colorado 80220, USA.
Dermody
T S
TS
Tyler
K L
KL
D000818:Animals; D016203:CDC2 Protein Kinase / Q000502:physiology*; D002453:Cell Cycle; D002460:Cell Line; D012089:Mammalian orthoreovirus 3 / Q000502:physiology*; D051379:Mice; D012088:Reoviridae Infections / Q000473:pathology / Q000821:virology*; D015398:Signal Transduction; D017361:Viral Nonstructural Proteins / Q000502:physiology*; D014779:Virus Replication
D017361:Viral Nonstructural Proteins; C071901:sigma 1NS protein, Reovirus; D016203:CDC2 Protein Kinase