Unexpected absence of the Epstein-Barr virus (EBV) lyLMP-1 open reading frame in tumor virus isolates: lack of correlation between Met129 status and EBV strain identity.
Unexpected absence of the Epstein-Barr virus (EBV) lyLMP-1 open reading frame in tumor virus isolates: lack of correlation between Met129 status and EBV strain identity.
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肿瘤病毒分离株中意外缺乏 Epstein-Barr 病毒 (EBV) lyLMP-1 开放阅读框：Met129 状态与 EBV 毒株身份之间缺乏相关性。
DOI：
10.1128/jvi.77.7.4415-4422.2003
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发表时间：
2003
影响因子：
5.4
通讯作者：
Martin,JenniferM
中科院分区：
文献类型：
--
作者：
Erickson,KimberlyD;Berger,Christoph;Coffin3rd,WilliamF;Schiff,Edwin;Walling,DennisM;Martin,JenniferM
EB病毒的裂解周期相关裂解潜伏膜蛋白-1(lyLMP-1)是致癌性LMP-1的氨基端截短形式。虽然lyLMP-1不具有LMP-1的S转化和信号转导活性，但我们最近报道，lyLMP-1可以负性调节LMP-1刺激的NF-κB的激活。EBV B95-8株编码的lyLMP-1蛋白起始于LMP-1开放阅读框(ORF)的蛋氨酸129(Met129)。最近关于B95-8 LMP-1 ORF中的Met129在EBV Akata株中不保守的报道促使我们筛选了一组EBV阳性细胞系来保守Met129和lyLMP-1的表达。我们发现，在测序的16株肿瘤相关病毒中，有15株在LMP-1ORF第129位编码ATT或ACC密码子而不是ATG，而含有缺失第129密码子ATG的肿瘤细胞株不表达lyLMP-1蛋白。相比之下，我们发现37名健康血清阳性捐赠者中有22名EBV DNA保留了Met129密码子。最后，lyLMP-1启动子在不同的EBV株中可变地出现，它的存在不能通过EBV株的同源性来预测。因此，Met129不是B95-8 EBV株所特有的，而是在几个进化上截然不同的EBV株的背景中发现的。从肿瘤中分离的EBV中没有它，增加了在EBV依赖的肿瘤中对Met129进行选择性压力的可能性。
The lytic cycle-associated lytic latent membrane protein-1 (lyLMP-1) of Epstein-Barr virus (EBV) is an amino-terminally truncated form of the oncogenic LMP-1. Although lyLMP-1 shares none of LMP-1's transforming and signal transducing activities, we recently reported that lyLMP-1 can negatively regulate LMP-1-stimulated NF-κB activation. The lyLMP-1 protein encoded by the B95-8 strain of EBV initiates from methionine 129 (Met129) of the LMP-1 open reading frame (ORF). The recent report that Met129 in the B95-8 LMP-1 ORF is not conserved in the Akata strain of EBV prompted us to screen a panel of EBV-positive cell lines for conservation of Met129 and lyLMP-1 expression. We found that 15 out of 16 tumor-associated virus isolates sequenced encoded an ATT or ACC codon in place of ATG in the LMP-1 ORF at position 129, and tumor cell lines harboring isolates lacking an ATG at codon 129 did not express the lyLMP-1 protein. In contrast, we found that EBV DNA from 22 out of 37 healthy seropositive donors retained the Met129 codon. Finally, the lyLMP-1 initiator occurs variably within distinct EBV strains and its presence cannot be predicted by EBV strain identity. Thus, Met129 is not peculiar to the B95-8 strain of EBV, but rather can be found in the background of several evolutionarily distinct EBV strains. Its absence from EBV isolates from tumors raises the possibility of selective pressure on Met129 in EBV-dependent tumors.