Polymorphism analysis of Epstein-Barr virus isolates from patients with cutaneous natural killer/T-cell lymphoproliferative disorders: A possible relation to the endemic occurrence of these diseases in Japan

Certain forms of cutaneous lymphomas in Asia are associated frequently with Epstein-Barr virus (EBV) infection, whereas such cases are less common in western countries. The virus-related peptides, ESV-determined nuclear antig en (EBNA)-2 and the latent membrane protein (LMP)-1, play an essential role in cell transformation. The polymorphisms of these EBV genes may be relate d to their transforming abilities. In order to clarify the viral subtype th at may be involved in the incidence of EBV-associated lymphomas, we analyze d the EBNA-2 and LMP-1 gene polymorphisms and mutations in healthy adults a nd in patients with EBV-associated cutaneous natural killer(NK)/T-cell lymp hoproliferative disorders in Japan. In EBV-related cutaneous lymphoprolifer ative disorders, EBV subtype 1 was found in all 15 cases, and 1 sample cont ained a dual infection with subtypes 1 and 2. All EBV isolates from our pat ients lost a Xho-1 site in exon 1 of the LMP-1 gene, and 7 of 13 cases had a Nco-1 site within the promoter region. All isolates without the LMP-1-Xho -1 site had a 30 bp deletion in the carboxy terminus of the LM P-l gene, ex cept for the isolate from a patient with angioimmunoblastic lymphadenophath y-like T-cell lymphoma in which a novel Nco-1 site was present in exon 1. E leven of fourteen throat washings from healthy adults which contained EBV-D NA harbored EBV subtype 1, and the EBNA2 region was not amplified in the ot her 3 samples. The Xho-1 site was lost in 12 (86%) of 14 isolates and the 3 0 bp deletion was present in 1 1 (78%) of 14 isolates from the throat washi ngs. The findings indicate that the predominant EBV isolate from Japanese h ealthy adults and patients with cutaneous NK/T-cell lymphoproliferative dis orders is subtype 1 with a 30 bp deletion and loss of a Xho-l site in the L MP-1 gene. Since previous data indicated that either subtype 1 or the 30 bp deletion variant possesses high tumorigenic activity, the prevalence of su btype 1 containing these mutations might be responsible for the high incide nce of EBV-associated lymphoproliferative disorders in Japan. (C) 2000 Wile y-Liss, Inc.