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J Virol, May 1998, p. 4038-4048, Vol. 72, No. 5
Department of Medicine, University of Wales
College of Medicine, Cardiff CF4 4XX, United
Kingdom,1 and
Microbiology and
Tumorbiology Center, Karolinska Institute, 17 177 Stockholm,
Sweden2
Received 17 September 1997/Accepted 2 February 1998
One group of sequence variants of Epstein-Barr virus is
characterized by a 10-amino-acid deletion within the CTAR-2 functional domain of the latent membrane protein, LMP1. A role for this deletion in enhancing the tumorigenicity of the viral oncogene in rodent fibroblasts was recently demonstrated. We examined the effect of this
deletion upon LMP1 function in four human lymphoid cell lines by using
three natural variants of LMP1: the prototype B95.8 gene and the CAO
and AG876 genes, both of which have codons 343 to 352 of the B95.8-LMP1
deleted. These experiments revealed that LMP1-mediated upregulation of
CD40 and CD54 was markedly impaired (by 60 to 90%) with CAO-LMP1
compared with B95.8-LMP1. In contrast, the function of AG876-LMP1 was
indistinguishable from that of B95.8-LMP1 in two lines and was only
slightly impaired in the other two lines. Activation of NF-
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
The 30-Base-Pair Deletion in Chinese Variants of the Epstein-Barr
Virus LMP1 Gene Is Not the Major Effector of Functional Differences
between Variant LMP1 Genes in Human Lymphocytes


B by
CAO-LMP1 was not impaired in any of the lines; rather, activation of an
NF-
B reporter by CAO-LMP1 was consistently about twofold greater
than the activation with B95.8- or AG876-LMP1. Therefore, while the
CAO-LMP1 is functionally distinct from the prototype B95.8-LMP1 in
human lymphocytes, the 10-amino-acid deletion appears not to be
directly responsible. This conclusion was confirmed by using a
B95.8-LMP1 mutant with codons 343 to 352 deleted and chimerae of CAO-
and B95.8-LMP1 in which the CTAR-2 domains of these genes were
exchanged. Sequences outside the CTAR-2 domain were implicated in the
distinct functional characteristics of CAO-LMP1 in human lymphoid
cells.
*
Corresponding author. Mailing address: Department of
Medicine, University of Wales College of Medicine, Tenovus Building, Heath Park, Cardiff CF4 4XX, United Kingdom. Phone: 44 1222 744624. Fax: 44 1222 743868. E-mail: RoweM{at}cf.ac.uk.
Present address: Department of Biological Sciences, Keele
University, Keele, Staffordshire ST5 5BG, United Kingdom.
Present address: Physiological Laboratory, University of
Liverpool, Liverpool L69 3BX, United Kingdom.
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