title: 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.
abstract: 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 LMP-1 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.
authors.affiliation: Laboratory of Immunopathology, University Institute of Pathology, Aarhus University Hospital, Denmark.
authors.forename: K
authors.initials: K
authors.lastname: Sandvej
authors.forename: J W
authors.initials: JW
authors.lastname: Gratama
authors.forename: M
authors.initials: M
authors.lastname: Munch
authors.forename: X G
authors.initials: XG
authors.lastname: Zhou
authors.forename: R L
authors.initials: RL
authors.lastname: Bolhuis
authors.forename: B S
authors.initials: BS
authors.lastname: Andresen
authors.forename: N
authors.initials: N
authors.lastname: Gregersen
authors.forename: S
authors.initials: S
authors.lastname: Hamilton-Dutoit
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D002460:Cell Line; D005814:Genes, Viral; D004854:Herpesvirus 4, Human / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D008214:Lymphocytes / Q000821:virology; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic / Q000235:genetics*; D016415:Sequence Alignment; D017421:Sequence Analysis; D014763:Viral Matrix Proteins / Q000235:genetics*
chemical_list: C037662:EBV-associated membrane antigen, Epstein-Barr virus; D014763:Viral Matrix Proteins