Selection pressure-driven evolution of the Epstein-Barr virus-encoded oncogene LMP1 in virus isolates from southeast Asia
Selection pressure-driven evolution of the Epstein-Barr virus-encoded oncogene LMP1 in virus isolates from southeast Asia
复制标题
DOI：
10.1128/jvi.78.13.7131-7137.2004
复制
发表时间：
2004-07-01
影响因子：
5.4
通讯作者：
Khanna, R
中科院分区：
文献类型：
--
作者：
Burrows, JM;Bromham, L;Khanna, R
东南亚人群中EB病毒（EBV）相关鼻咽癌（NPC）的地理分布限制表明，病毒和宿主遗传学都可能影响疾病风险。虽然易感基因位点已被定位在人类基因组中，但病毒遗传学在NPC局灶性分布中的作用仍然是一个谜。在这里，我们报告了一个NPC相关的病毒癌基因，LMP 1的分子系统发育分析，在一个大面板的EB病毒分离株从东南亚和巴布亚新几内亚，非洲和澳大利亚，世界上的地区，NPC是和不是地方病，分别。该分析显示，LMP 1序列显示出独特的地理结构，表明东南亚分离株已进化为不同于巴布亚新几内亚、非洲和澳大利亚分离株的谱系。此外，似然比检验显示，东南亚血统的LMP 1序列的C末端处于显著的正选择压力下，特别是在C末端激活区域内的一些位点。我们还提出的证据表明，虽然LMP 1的N末端和跨膜区已经经历了重组，该基因的C-末端区域已经演变没有任何重组的历史。基于这些观察结果，我们推测，选择压力可能是驱动LMP 1序列在病毒分离株从东南亚走向更恶性的表型，从而影响NPC在该地区的地方性分布。
The geographically constrained distribution of Epstein-Barr virus (EBV)-associated nasopharyngeal carcinoma (NPC) in southeast Asian populations suggests that both viral and host genetics may influence disease risk. Although susceptibility loci have been mapped within the human genome, the role of viral genetics in the focal distribution of NPC remains an enigma. Here we report a molecular phylogenetic analysis of an NPC-associated viral oncogene, LMP1, in a large panel of EBV isolates from southeast Asia and from Papua New Guinea, Africa, and Australia, regions of the world where NPC is and is not endemic, respectively. This analysis revealed that LMP1 sequences show a distinct geographic structure, indicating that the southeast Asian isolates have evolved as a lineage distinct from those of Papua New Guinea, African, and Australian isolates. Furthermore, a likelihood ratio test revealed that the C termini of the LMP1 sequences of the southeast Asian lineage are under significant positive selection pressure, particularly at some sites within the C-terminal activator regions. We also present evidence that although the N terminus and transmembrane region of LMP1 have undergone recombination, the C-terminal region of the gene has evolved without any history of recombination. Based on these observations, we speculate that selection pressure may be driving the LMP1 sequences in virus isolates from southeast Asia towards a more malignant phenotype, thereby influencing the endemic distribution of NPC in this region.