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The Epstein-Barr virus protein BRLF1 activates S phase entry through E2F1 induction
J J Swenson1, A E Mauser, W K Kaufmann
1Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina 27599, USA.
Journal of Virology
|July 10, 1999
Summary
Epstein-Barr Virus (EBV) protein BRLF1 drives infected cells into S phase, increasing E2F1 levels. This EBV activation of E2F1 is crucial for viral replication and causes cell apoptosis.
Area of Science:
- Virology
- Molecular Biology
- Cell Biology
Background:
- Epstein-Barr Virus (EBV) controls latent to lytic replication via transactivators.
- DNA viruses often manipulate host cell cycle proteins for replication.
- The role of EBV's BRLF1 protein in cell cycle regulation was investigated.
Purpose of the Study:
- To investigate the effect of EBV's BRLF1 protein on host cell cycle progression.
- To determine how BRLF1 influences key cell cycle regulatory proteins.
- To understand the implications of BRLF1-induced cell cycle changes for EBV replication.
Main Methods:
- Infection of human fibroblasts and epithelial cells with a replication-deficient adenovirus expressing BRLF1 (AdBRLF1).
- Analysis of cell cycle progression, including S phase entry.
- Quantification of cell cycle regulatory proteins (E2F1, E2F4, Rb, p107, p130, p53, p21) using Western blotting and electrophoretic mobility shift assays.
Main Results:
- BRLF1 expression induced S phase entry in quiescent and epithelial cells.
- AdBRLF1 infection led to increased levels of E2F1 and decreased levels of Rb, p107, and p130.
- Elevated free E2F1 levels correlated with increased p53 and p21 expression, leading to apoptosis.
Conclusions:
- EBV BRLF1 protein manipulates the host cell cycle by activating E2F1.
- BRLF1-induced E2F1 activation promotes S phase entry and apoptosis in infected cells.
- Activation of E2F1 by BRLF1 is likely essential for efficient EBV lytic replication, particularly for viral DNA polymerase expression.