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Journal of Virology, June 1999, p. 4678-4688, Vol. 73, No. 6
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Control of Cell Cycle Entry and Apoptosis in B Lymphocytes Infected by Epstein-Barr Virus

Lindsay C. Spender,1 Emma J. Cannell,1,dagger Martine Hollyoake,1 Barbara Wensing,1 Jonathan M. Gawn,1 Matthew Brimmell,1 Graham Packham,1,2 and Paul J. Farrell1,2,*

Ludwig Institute for Cancer Research1 and Virology and Cell Biology Section,2 Imperial College School of Medicine, St. Mary's Campus, London W2 1PG, United Kingdom

Received 23 October 1998/Accepted 23 February 1999

Infection of human B cells with Epstein-Barr virus (EBV) results in activation of the cell cycle and cell growth. To interpret the mechanisms by which EBV activates the cell, we have assayed many proteins involved in control of the G0 and G1 phases of the cell cycle and regulation of apoptosis. In EBV infection most of the changes, including the early induction of cyclin D2, are dependent on expression of EBV genes, but an alteration in the E2F-4 profile was partly independent of viral gene expression, presumably occurring in response to signal transduction activated when the virus binds to its receptor, CD21. By comparing the expression of genes controlling apoptosis, including those encoding several members of the BCL-2 family of proteins, the known relative resistance of EBV-immortalized B-cell lines to apoptosis induced by low serum was found to correlate with expression of both BCL-2 and A20. A20 can be regulated by the NF-kappa B transcription factor, which is known to be activated by the EBV LMP-1 protein. Quantitative assays demonstrated a direct temporal relationship between LMP-1 protein levels and active NF-kappa B during the time course of infection.


* Corresponding author. Mailing address: Ludwig Institute for Cancer Research, Imperial College School of Medicine, St. Mary's Campus, Norfolk Place, London W2 1PG, United Kingdom. Phone: 44 171 724 5522. Fax: 44 171 724 8586. E-mail: p.farrell{at}ic.ac.uk.

dagger Present address: Institute for Cancer Research, Chester Beatty Laboratories, London SW3 6JB, United Kingdom.


Journal of Virology, June 1999, p. 4678-4688, Vol. 73, No. 6
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.



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