Sequence variations of Epstein-Barr virus LMP1 gene in nasal NK/T-cell lymphoma
Sequence variations of Epstein-Barr virus LMP1 gene in nasal NK/T-cell lymphoma
复制标题
DOI：
10.1007/s11262-006-0008-5
复制
发表时间：
2007-01-01
期刊：
影响因子：
1.6
通讯作者：
Harabuchi, Yasuaki
中科院分区：
文献类型：
--
作者：
Nagamine, Masayoshi;Takahara, Miki;Harabuchi, Yasuaki
鼻腔自然杀伤(NK)/T细胞淋巴瘤是一种具有独特免疫表型的特殊淋巴瘤。在病因学上，作者先前首次证明在该淋巴瘤中存在EB病毒(EBV)基因组及其产物(《柳叶刀》1990；335)。提示一些序列变异，如30bp缺失和多个碱基替换，以及人类白细胞抗原A2限制性CTL表位的氨基酸变化，与肿瘤致瘤性的增加和免疫识别能力的降低有关。在本研究中，我们用聚合酶链式反应(PCR)方法测定了从7例鼻NK/T细胞淋巴瘤患者中分离的LMP1的全长序列，并将其与文献报道的序列进行了比较。在羧基末端，所有7例患者都有4个拷贝的11个氨基酸重复(密码子254-302)和对应于B95-8毒株密码子343-352的30个碱基缺失。在核因子-kB激活区域内，7例患者均表现出PXQXT(密码子204-208)任一位密码子189(Gln To Pro)、192(Ser To Thr)和212(Gly To Ser)的氨基酸变化。在主要的人类白细胞抗原A2限制性T细胞表位序列YLLEMLWRL(密码子125-133)中，7例患者均表现出第126位密码子(Leu-to Phe)和129位(Met-Ile)的氨基酸变化。在ALLVLYSFA(密码子51-59)、VLFIFGCLL(密码子110-118)和WLLL-Flail(密码子173-181)表位中，有几位患者分别在密码子59(Ala到Gly)、Val(Val到Leu)和174(Leu到Ile)发生了新的氨基酸变化。虽然目前尚不清楚LMP1基因在鼻NK/T细胞淋巴瘤中最具特异性和生物学意义的变异是什么，但该序列数据可能对鼻NK/T细胞淋巴瘤的发病机制和EBV分子流行病学的研究有价值。
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 WLLL-FLAIL (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.