Infection with Vaccinia Virus Alters Regulation of Cell Cycle Progression

The effect of vaccinia virus (VV) on cell cycle progression and its regulators was studied. Infected cultures showed significantly increased transit through G₁, decreasing the percentage of cells in G₁ and increasing the percentage in S phase. The numbers of cells in G₂/M were not affected. Because of the increased S-phase fraction at the expense of G₁, expression of cyclins and cyclin-dependent kinases (Cdks) that regulate cell cycle checkpoints was examined. Transcripts for cyclins A and B, Cdk2, and Cdc2 were decreased in VV-infected cells as infection progressed. The amounts of p53 and p27 proteins decreased after 12 and 24 h of infection, respectively. The Cdc2 and Cdk2 protein levels were decreased with increasing time after infection. Taken together, these findings would be expected to lead to more cells in S phase and G₂/M, as was observed. Therefore, VV actively modulates expression of cellular regulators of the cell cycle and alters cell cycle progression.