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Comparative effects of virulent and avirulent poxviruses on cell cycle progression
1Department of Pathology, Anatomy, and Cell Biology, Jefferson Medical College, Philadelphia, Pennsylvania 19107, USA.
Abstract:
We studied the impact of tumorigenic poxviral infection on key regulators of cell cycle progression. Malignant fibroma virus (MV) is a virulent poxvirus that causes severe immunological impairment in vivo and in vitro. It also directs expression of important cellular regulatory proteins, such as p53. Its avirulent relative, Shope fibroma virus (SFV), has little effect on the immune system or p53. Accordingly we examined the effects of MV and SFV on the cell cycle in RK-13 rabbit kidney fibroblasts. MV caused an accumulation of cells in G2/M phase and decreased the percentage of cells in G0/G1. Prolongation of G2/M phase was associated with increased levels of cyclin B protein, decreases in cyclin A and cdc2 proteins, and diminished cdc2 activity. In contrast SFV did not affect cellular cycling detectably. SFV infection was accompanied by large increases in cyclin A and cdc2 proteins and increased cdc2 activity. Thus alterations in cell cycle transit during virus infection may reflect active direction in which virus induces changes in cell cycle regulators. Such changes may be important in the differences in virulence between MV and SFV.
Insights
Malignant fibroma virus (MV) halts cell cycle progression, impacting key regulators like cyclin B. In contrast, Shope fibroma virus (SFV) promotes cell cycle activity, highlighting distinct viral effects on host cell mechanisms.
Area of Science:
- Virology
- Cell Biology
- Molecular Biology
Background:
- Poxviral infections can significantly impact host cell functions.
- Malignant fibroma virus (MV) is a virulent poxvirus causing immunological impairment and affecting cellular proteins like p53.
- Shope fibroma virus (SFV) is an avirulent relative with minimal effects on the immune system or p53.
Purpose of the Study:
- To investigate the impact of tumorigenic poxviral infection on cell cycle regulators.
- To compare the effects of virulent (MV) and avirulent (SFV) fibroma viruses on cell cycle progression in rabbit kidney fibroblasts (RK-13).
Main Methods:
- Infection of RK-13 cells with MV and SFV.
- Analysis of cell cycle distribution using flow cytometry.
- Quantification of cell cycle regulatory proteins (cyclin B, cyclin A, cdc2) via Western blotting.
- Assay of cdc2 kinase activity.
Main Results:
- MV infection led to G2/M phase accumulation and decreased G0/G1 phase cells.
- MV infection increased cyclin B levels, decreased cyclin A and cdc2 proteins, and reduced cdc2 activity.
- SFV infection did not significantly alter cell cycling.
- SFV infection increased cyclin A and cdc2 protein levels and enhanced cdc2 activity.
Conclusions:
- Viral infections actively modulate cell cycle regulators.
- Distinct alterations in cell cycle transit during MV and SFV infections correlate with differences in their virulence.
- These findings suggest that virus-induced changes in cell cycle regulation are critical for determining viral pathogenicity.