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Journal of Virology, February 1999, p. 965-975, Vol. 73, No. 2
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
Epstein-Barr Virus Nuclear Antigen 1 Sequences in
Endemic and Sporadic Burkitt's Lymphoma Reflect Virus Strains
Prevalent in Different Geographic Areas
G.
Habeshaw,1,2
Q. Y.
Yao,2
A. I.
Bell,2
D.
Morton,3 and
A.
B.
Rickinson2,*
Department of
Pathology1 and
CRC Institute for Cancer
Studies,2 University of Birmingham,
Edgbaston, Birmingham B15 2TA, United Kingdom, and
Kuluva
Church of Uganda Hospital, Arua, Uganda3
Received 27 August 1998/Accepted 20 October 1998
The Epstein-Barr virus (EBV) nuclear antigen EBNA1 is the only
viral protein detectably expressed in virus genome-positive Burkitt's
lymphoma (BL); recent work has suggested that viral strains with
particular EBNA1 sequence changes are preferentially associated with
this tumor and that, within a patient, the tumor-associated variant may
have arisen de novo as a rare mutant of the dominant preexisting EBV
strain (K. Bhatia, A. Raj, M. J. Gutierrez, J. G. Judde, G. Spangler, H. Venkatesh, and I. T. Magrath, Oncogene 13:177-181,
1996). In the present work we first study 12 BL patients and show that
the virus strain in the tumor is identical in EBNA1 sequence and that
it is matched at several other polymorphic loci to the dominant strain
rescued in vitro from the patient's normal circulating B cells. We
then analyze BL-associated virus strains from three different
geographic areas (East Africa, Europe, and New Guinea) alongside virus
isolates from geographically matched control donors by using sequence
changes in two separate regions of the EBNA1 gene (N-terminal codons 1 to 60 and C-terminal codons 460 to 510) to identify the EBNA1 subtype
of each virus. Different geographic areas displayed different spectra
of EBNA1 subtypes, with only limited overlap between them; even type 2 virus strains, which tended to be more homogeneous than their type 1 counterparts, showed geographic differences at the EBNA1 locus. Most
importantly, within any one area the EBNA1 subtypes associated with BL
were also found to be prevalent in the general population. We therefore find no evidence that Burkitt lymphomagenesis involves a selection for
EBV strains with particular EBNA1 sequence changes.
*
Corresponding author. Mailing address: CRC Institute
for Cancer Studies, University of Birmingham, Edgbaston, Birmingham B15 2TA, United Kingdom. Phone: 44-121-414-4492. Fax: 44-121-414-4486. E-mail: williamsd{at}cancer.bham.ac.uk.
Journal of Virology, February 1999, p. 965-975, Vol. 73, No. 2
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
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