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Journal of Virology, August 1999, p. 6540-6550, Vol. 73, No. 8
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
The Epstein-Barr Virus Protein BRLF1 Activates S
Phase Entry through E2F1 Induction
Jennifer J.
Swenson,1
Amy E.
Mauser,1
William K.
Kaufmann,2,3 and
Shannon C.
Kenney1,2,*
Lineberger Comprehensive Cancer
Center,1 Department of Medicine and
Microbiology,2 and Department of
Pathology,3 University of North Carolina, Chapel
Hill, North Carolina 27599
Received 17 November 1998/Accepted 22 April 1999
The Epstein-Barr Virus (EBV) immediate-early protein BRLF1 is one
of two transactivators which mediate the switch from latent to lytic
replication in EBV-infected cells. DNA viruses often modulate the
function of critical cell cycle proteins to maximize the efficiency of
virus replication. Here we have examined the effect of BRLF1 on cell
cycle progression. A replication-deficient adenovirus expressing BRLF1
(AdBRLF1) was used to infect normal human fibroblasts and various
epithelial cell lines. BRLF1 expression induced S phase entry in
contact-inhibited fibroblasts and in the human osteosarcoma cell line
U-2 OS. AdBRLF1 infection produced a dramatic increase in the level of
E2F1 but not E2F4. In contrast, the levels of Rb, p107, and p130 were
decreased in AdBRLF1-infected cells. Electrophoretic mobility shift
assays confirmed an increased level of free E2F1 in the
AdBRLF1-infected human fibroblasts. Consistent with the previously
described effect of E2F1, AdBRLF1-infected fibroblasts had increased
levels of p53 and p21 and died by apoptosis. BRLF1-induced activation
of E2F1 may be required for efficient EBV lytic replication, since at
least one critical viral replication gene (the viral DNA polymerase) is
activated by E2F (C. Liu, N. D. Sista, and J. S. Pagano,
J. Virol. 70:2545-2555, 1996).
*
Corresponding author. Mailing address: Lineberger
Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599. Phone: (919) 966-1248. Fax: (919) 966-8212. E-mail: shann{at}med.unc.edu.
Journal of Virology, August 1999, p. 6540-6550, Vol. 73, No. 8
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
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