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Sequence Analysis of the Epstein-Barr Virus (EBV) Latent Membrane Protein-1 Gene and Promoter Region: Identification of Four Variants Among Wild-Type EBV Isolates
Kristian Sandvej,
Jan W. Gratama,
Mette Munch,
Xiao-Ge Zhou,
Reinder L.H. Bolhuis,
Brage Storstein Andresen,
Niels Gregersen, and
Stephen Hamilton-Dutoit
From Laboratory of Immunopathology, University Institute of Pathology, Aarhus University Hospital; Centre for Medical Molecular Biology, Aarhus University Hospital and Faculty of Health Science, Skejby Hospital; the Department of Medical Microbiology and Immunology, University of Aarhus, Aarhus, Denmark; and the Department of Clinical and Tumor Immunology, Dr Daniel den Hoed Kliniek, Rotterdam, The Netherlands.
Sequence variations in the Epstein-Barr virus (EBV) encoded latent membrane protein-1 (LMP-1) gene have been described in a Chinese nasopharyngeal carcinoma-derived isolate (CAO), and in viral isolates from various EBV-associated tumors. It has been suggested that these genetic changes, which include loss of a Xho I restriction site (position 169425) and a C-terminal 30-base pair (bp) deletion (position 168287-168256), define EBV genotypes associated with increased tumorigenicity or with disease among particular geographic populations. To determine the frequency of LMP-1 variations in European wild-type virus isolates, we sequenced the LMP1 promoter and gene in EBV from lymphoblastoid cell lines from healthy carriers and patients without EBV-associated disease. Sequence changes were often present, and defined at least four main groups of viral isolates, which we designate Groups A through D. The widespread prevalence of LMP-1 sequence variations, particularly the Xho I polymorphism and the 30-bp deletion, indicate that they cannot be used as simple markers for oncogenic viruses related to particular forms of EBV-associated tumor. Several of the structural changes detected occur, however, at sites where they may affect transcription, translation, or function of LMP-1. Future in vitro studies should aim to establish the functional importance of variations at these sites.
Blood, Vol. 90 No. 1 (July 1), 1997:
pp. 323-330
© 1997 by The American Society of Hematology.
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