title: EBNA-1 sequence variation in Danish and Chinese EBV-associated tumours: evidence for geographical polymorphism but not for tumour-specific subtype restriction.
abstract: The Epstein-Barr virus (EBV) nuclear antigen (EBNA)-1 is consistently expressed in EBV-associated tumours. Recently, EBNA-1 carboxy (C)-terminal sequence variants have been described based on the amino acid signature at codon 487, and designated prototype (P)-ala (identical to prototype B95.8 strain), P-thr, variant (V)-val, V-leu, and V-pro. These studies suggest that certain EBNA-1 variants show selective cell tropism and may be preferentially associated with different EBV-positive malignancies; for example, in contrast to P-ala subtypes, V-val appeared to be restricted to the oral compartment and to be associated with undifferentiated nasopharyngeal carcinoma (NPC). To test the hypothesis that V-val subtypes are restricted in distribution, EBNA-1 variants were investigated in NPC and throat washings (TWs) from a low (Denmark) and a high (China) NPC risk area. For comparison, cases of Hodgkin's disease (HD) were also studied. V-val was found to be the dominant EBNA-1 subtype, not only in Chinese TWs and NPC biopsies, but also in Chinese HD. Furthermore, V-val was not detected in any of the Danish NPC biopsies or TW samples. These findings show that V-val is not associated with NPC, nor is it restricted to the oral compartment, but rather that it represents a dominant Asian EBNA-1 subtype, both in EBV-associated malignancies and in the general population.
authors.affiliation: Institute of Pathology, Aarhus University Hospital and the Faculty of Health Sciences, Denmark.
authors.forename: K
authors.initials: K
authors.lastname: Sandvej
authors.forename: X G
authors.initials: XG
authors.lastname: Zhou
authors.forename: S
authors.initials: S
authors.lastname: Hamilton-Dutoit
mesh_terms: D002681:China; D003718:Denmark; D019309:Epstein-Barr Virus Nuclear Antigens / Q000235:genetics*; D004854:Herpesvirus 4, Human / Q000235:genetics; D006689:Hodgkin Disease / Q000235:genetics*; D006801:Humans; D009154:Mutation / Q000235:genetics; D009303:Nasopharyngeal Neoplasms / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012344:RNA, Transfer, Ala / Q000235:genetics; D012356:RNA, Transfer, Leu / Q000235:genetics; D012361:RNA, Transfer, Pro / Q000235:genetics; D012363:RNA, Transfer, Thr / Q000235:genetics; D012366:RNA, Transfer, Val / Q000235:genetics; D020539:Sequence Analysis, Protein
chemical_list: D019309:Epstein-Barr Virus Nuclear Antigens; D012344:RNA, Transfer, Ala; D012356:RNA, Transfer, Leu; D012361:RNA, Transfer, Pro; D012363:RNA, Transfer, Thr; D012366:RNA, Transfer, Val