EBNA-1 sequence variation in Danish and Chinese EBV-associated tumours: evidence for geographical polymorphism but not for tumour-specific subtype restriction

J Pathol. 2000 Jun;191(2):127-31. doi: 10.1002/(SICI)1096-9896(200006)191:2<127::AID-PATH614>3.0.CO;2-E.


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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • China
  • Denmark
  • Epstein-Barr Virus Nuclear Antigens / genetics*
  • Herpesvirus 4, Human / genetics
  • Hodgkin Disease / genetics*
  • Humans
  • Mutation / genetics
  • Nasopharyngeal Neoplasms / genetics*
  • Polymerase Chain Reaction
  • Polymorphism, Genetic*
  • RNA, Transfer, Ala / genetics
  • RNA, Transfer, Leu / genetics
  • RNA, Transfer, Pro / genetics
  • RNA, Transfer, Thr / genetics
  • RNA, Transfer, Val / genetics
  • Sequence Analysis, Protein


  • Epstein-Barr Virus Nuclear Antigens
  • RNA, Transfer, Ala
  • RNA, Transfer, Leu
  • RNA, Transfer, Pro
  • RNA, Transfer, Thr
  • RNA, Transfer, Val