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

The Epstein-Barr virus (EBV) nuclear antigen (EBNA)-1 is consistently expre ssed in EBV-associated tumours. Recently, EBNA-1 carboxy (C)-terminal seque nce 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 cer tain EBNA-1 variants show selective cell tropism and may be preferentially associated with different EBV-positive malignancies; for example, in contra st to P-ala subtypes, V-val appeared to be restricted to the oral compartme nt and to be associated with undifferentiated nasopharyngeal carcinoma (NPC ). To test the hypothesis that V-val subtypes are restricted in distributio n, 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 dominan t EBNA-1 subtype, not only in Chinese TWs and NPC biopsies, but also in Chi nese HD. Furthermore, V-val was not detected in any of the Danish NPC biops ies or TW samples. These findings show that V-val is not associated with NP C, nor is it restricted to the oral compartment, but rather that it represe nts a dominant Asian EBNA-1 subtype, both in EBV-associated malignancies an d in the general population. Copyright (C) 2000 John Wiley & Sons, Ltd.