Sequence variations of Epstein-Barr virus LMP1 gene in nasal NK/T-cell lymphoma.
Nasal natural killer (NK)/T-cell lymphoma is a peculiar lymphoma with an unique immunophenotype. Etiologically, the authors previously first demonstrated the presence of Epstein-Barr virus (EBV) genomes and their products in this lymphoma (Lancet 1990; 335). It is suggested that some of sequence variations such as a 30-bp deletion and multiple base substitutions and as amino acid changes at HLA-A2 restricted CTL epitopes were associated with an increase in tumorigenicity and with a decrease in immune recognition. In this study, we determined full-length of LMP1 sequence isolated from 7 patients with nasal NK/T-cell lymphoma using polymerase chain reaction (PCR) method and compared the sequences with those referred to previous reports. In the carboxyl-terminal site, all 7 patients showed 4 copies of the 11 amino acids repeat (codon 254-302) and 30-bp deletion corresponding to codon 343-352 of the B95-8 strain. Within the NF-kB-activating domains, all 7 patients showed amino acid changes at codon 189 (Gln to Pro), 192 (Ser to Thr) and 212 (Gly to Ser) on either site of the PXQXT (codon 204-208) motif. In the major HLA-A2 restricted T-cell epitope sequence YLLEMLWRL (codon 125-133), all 7 patients showed amino acid changes at codon 126 (Leu to Phe) and 129 (Met to Ile). In the epitopes ALLVLYSFA (codon 51-59), VLFIFGCLL (codon 110-118) and WLLLFLAIL (codon 173-181), several patients showed novel amino acid changes at codon 59 (Ala to Gly), 110 (Val to Leu) and 174 (Leu to Ile), respectively. Although it is still not clear what the most specific and biologic variation of LMP1 gene in nasal NK/T-cell lymphoma is, the sequence data may be valuable on the study for pathogenesis of nasal NK/T-cell lymphoma and EBV molecular epidemiology.
Nagamine
Masayoshi
M
Department of Otolaryngology-Head and Neck Surgery, Asahikawa Medical University, Midorigaoka E2-1-1-1, Asahikawa, 078-8510, Japan.
Takahara
Miki
M
Kishibe
Kan
K
Nagato
Toshihiro
T
Ishii
Hideyuki
H
Bandoh
Nobuyuki
N
Ogino
Takeshi
T
Harabuchi
Yasuaki
Y
D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D001483:Base Sequence; D020134:Catalytic Domain; D004262:DNA Restriction Enzymes / Q000378:metabolism; D005260:Female; D014644:Genetic Variation; D004854:Herpesvirus 4, Human / Q000235:genetics*; D006801:Humans; D007694:Killer Cells, Natural / Q000473:pathology / Q000821:virology; D008228:Lymphoma, Non-Hodgkin / Q000821:virology*; D016399:Lymphoma, T-Cell / Q000821:virology*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009297:Nasal Mucosa / Q000473:pathology / Q000821:virology*; D014763:Viral Matrix Proteins / Q000235:genetics*
C037662:EBV-associated membrane antigen, Epstein-Barr virus; D014763:Viral Matrix Proteins; D004262:DNA Restriction Enzymes