Limited sequence heterogeneity of Epstein-Barr virus nuclear antigen 1 in benign and malignant EBV-Associated disorders

Background: The Epstein-Barr virus (EBV) nuclear antigen 1 (EBNA-1) is esse ntial for replication and maintenance of circular EBV genomes in latently i nfected B lymphocytes and is the only EBV protein expressed in nearly all c ells carrying the virus. EBNA-1 is suggested to be oncogenic in vivo since its expression induces B-cell neoplasia in transgenic mice. Patients, Materials and Methods: EBV wild-type isolates from ten malignant tumors and from 15 children with various benign EBV-associated disorders we re examined for the presence of EBNA-1 variant strains by PCR and sequencin g. Results: One isolate harbored both the B95-8-like and a variant sequence wi thin the C-terminus of the EBNA-1 gene. All other isolates (n = 24) reveale d clustered nucleic acid sequence alterations within the EBNA-1 gene, which led to amino acid exchanges at positions 524, 563, 574, 585, 594 and 595 F ew isolates exhibited additional amino acid exchanges at positions 564, 571 or 588. Conclusions: The observed EBNA-1 sequence variation pattern seems not to be restricted to a certain EBV-associated disease or tumor type. The EBNA-1 v ariant strains reported here may reflect the most prevalent EBV strains in the exposed population. In none of all the cases studied so far did the seq uence alteration affect any known functionally crucial amino acids in the c ore domain of EBNA-1. This suggests that strict conservation of most of the C-terminal portion of EBNA-1 sequence may be essential for survival of EBV in the infected host.