Signature amino acid changes in latent membrane protein 1 distinguish Epstein-Barr virus strains

Sequence variations in the Epstein-Barr virus (EBV) latent membrane protein 1 gene have been described in numerous EBV-associated tumors with some of these variations, most notably a 30-base pair deletion in the cytoplasmic c arboxyl-terminal domain, suggested as associated with an increase in tumori genicity. In this study, EBV DNA sequence was determined from 92 tissue spe cimens or cell lines, including nasopharyngeal carcinoma, oral hairy leukop lakia, posttransplant lymphoma, post-transplant without pathology mononucle osis, Burkitt's lymphoma, parotid tumor, and normal from distinct geographi cal regions. The amino- and carboxyl-terminal sequences and, in some cases, the full-length sequences of latent membrane protein 1 were determined. Ch aracteristic sequence patterns distinguished strains, with the carboxyl-ter minal sequence being the most informative in distinguishing among the strai ns. Phylogenetic relationships between strains were determined, as were sig nature amino acid changes that discriminate between them. A correlation bet ween strain and disease or strain and geographic location was not detected. The sequence variation and signature sequences identified at least seven d istinct strains, as well as hybrid strains that apparently result from reco mbination. (C) 1999 Academic Press.