SEQUENCE-ANALYSIS OF THE EPSTEIN-BARR-VIRUS (EBV) LATENT MEMBRANE PROTEIN-1 GENE AND PROMOTER REGION - IDENTIFICATION OF 4 VARIANTS AMONG WILD-TYPE EBV ISOLATES

Sequence variations in the Epstein-Barr virus (EBV) encoded latent mem brane protein-1 (LMP-1) gene have been described in a Chinese nasophar yngeal carcinoma-derived isolate (CAO), and in viral isolates from var ious EBV-associated tumors. It has been suggested that these genetic c hanges, which include loss of a Xho I restriction site (position 16942 5) and a C-terminal 30-base pair (bp) deletion (position 168287-168256 ), define EBV genotypes associated with increased tumorigenicity or wi th disease among particular geographic populations. To determine the f requency of LMP-1 variations in European wild-type virus isolates, we sequenced the LMP-1 promoter and gene in EBV from lymphoblastoid cell lines from healthy carriers and patients without EBV-associated diseas e. 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 X ho I polymorphism and the 30-bp deletion, indicate that they cannot be used as simple markers for oncogenic viruses related to particular fo rms of EBV-associated tumor. Several of the structural changes detecte d occur, however, at sites where they may affect transcription, transl ation, or function of LMP-1. Future in vitro studies should aim to est ablish the functional importance of variations at these sites. (C) 199 7 by The American Society of Hematology.