PDF(Pubmed)
Abstract：
The critical Epstein‒Barr virus (EBV)-encoded latent membrane protein 1 (LMP-1) and BamHI fragment H rightward open reading frame 1 (BHRF-1) genes affect EBV-mediated malignant transformation and virus replication during EBV infection. Therefore, these two genes are considered ideal targets for EBV vaccine development. However, gene mutations in LMP-1 and BHRF-1 in different cohorts may affect the biological functions of EBV, which would seriously hinder development of personalized vaccines for EBV. In the present study, by performing nested polymerase chain reaction (nested PCR) and DNA sequence techniques, we analyzed the nucleotide variability and phylogeny of LMP-1 containing a 30 bp deletion region (del-LMP-1) and BHRF-1 in EBV-infected patients (N = 382) and healthy persons receiving physical examination (N = 98; defined as the control group) in Yunnan Province, China. Three BHRF-1 subtypes were identified in this study: 79V88V, 79L88L, and 79V88L, with mutation frequencies of 58.59%, 24.24%, and 17.17%, respectively. Compared with the control group, the distribution of BHRF-1 subtypes of the three groups showed no significant difference, suggesting that BHRF-1 is highly conserved in EBV-related samples. In addition, a short fragment of del-LMP-1 was found in 133 cases, and the nucleotide variation rate was 87.50% (133/152). For del-LMP-1, a significant distribution in three groups was detected, as characterized by a high mutation rate. In conclusion, our study illustrates gene variability and mutations of EBV-encoded del-LMP-1 and BHRF-1 in clinical samples. Highly mutated LMP-1 might be associated with various types of EBV-related diseases, indicating that BHRF-1 combined with LMP-1 may be used as an ideal target for development of EBV personalized vaccines.
摘要：
关键的爱泼斯坦-巴尔病毒（EBV）编码的潜伏膜蛋白1（LMP-1）和BamHI片段H向右开放阅读框1（BHRF-1）基因影响EBV介导的恶性转化和病毒复制感染。因此,这两个基因被认为是EBV疫苗开发的理想靶标。然而,不同队列中LMP-1和BHRF-1基因突变可能影响EBV的生物学功能,这将严重阻碍EBV个性化疫苗的开发。在本研究中,通过执行巢式聚合酶链反应（巢式PCR）和DNA序列技术，我们分析了云南省EBV感染患者（N=382）和健康人（N=98；定义为对照组）中含有30bp缺失区的LMP-1（del-LMP-1）和BHRF-1的核苷酸变异性和系统发育，中国。在这项研究中确定了三种BHRF-1亚型：79V88V，79L88L,和79V88L，突变频率为58.59%,24.24%,和17.17%，分别。与对照组相比,三组间BHRF-1亚型分布无显著性差异,提示BHRF-1在EBV相关样本中高度保守。此外,在133例病例中发现了del-LMP-1的短片段，核苷酸变异率为87.50%(133/152)。对于del-LMP-1，检测到三组中的显着分布，具有高突变率的特点。总之,我们的研究说明了临床样本中EBV编码的del-LMP-1和BHRF-1的基因变异性和突变。高度突变的LMP-1可能与各种类型的EBV相关疾病有关，提示BHRF-1与LMP-1联合可能成为开发EBV个体化疫苗的理想靶点。
