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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,
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-
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-
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.

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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