新疆南部地区维吾尔族妇女宫颈癌组织中人乳头状瘤病毒16型L1基因突变谱分析

目的 探讨新疆南部地区维吾尔族妇女宫颈癌组织中人乳头状瘤病毒16型L1基因的变异，并预测L1蛋白的功能变化。方法 从19份中国新疆南部地区维吾尔族妇女宫颈癌活检组织标本中提取DNA，以此DNA为模板，PCR扩增HPV16 L1全长基因，PCR产物直接测序或克隆后测序，分析新疆维吾尔族妇女宫颈癌组织HPV16 L1基因多态性及HPV16 L1蛋白功能的变化。结果 PCR检测结果显示宫颈癌组织中HPV16 L1阳性率为84．21％(16／19)；测序和序列分析表明L1基因核苷酸多处发生变异，并引起编码氨基酸的变异，L1基因在核苷酸水平形成上6种突变模式(XJL1-1～XJL1-6)，各模式与HPV16原型比较，同源性在99．69％～99．87％之间。XJL1-1发生的4处变异是所有变异序列所共有的，XJL1-2～XJL1-6在XJL1-1变异的基础上增加了不同的变异；在氨基酸水平上形成4种突变模式，其中XJL1—1／2／3突变模式占76．92％(8／13)，是突变的主流模式；以上突变引起HPV16 L1蛋白疏水性和抗原性的改变，继而改变了L1蛋白的结构及功能。结论中国新疆南部地区维吾尔族妇女宫颈癌患者组织中HPV16 L1基因发生多位点变异，并形成多种突变模式和突变的主流模式；这些突变引起HPV16 L1蛋白疏水性和抗原性的改变，提示HPV16 L1基因突变可能与HPV16的种系发生以及病毒逃避机体免疫识别有关。

Mutations of human papillomavirus (HPV) 16 type L1 genes from cervical carcinoma biopsies in southern Xinjiang Uygur women

OBJECTIVE: To study the mutations of Human Papillomavirus (HPV) 16 type L1 genes of cervical carcinoma biopsies from Uygur women in Southern Xinjiang, and analyze changes of L1 protein function. METHODS: The tissue DNA was extracted from cervical carcinoma biopsies. HPV16 L1 genes were amplified by PCR from the DNA HPV16 type L1 genes were sequenced and analyzed. RESULTS: The result of PCR showed that the positive rate of HPV16 L1 was 84.21% (16/19). These DNA were sequenced, and we found some mutations in comparison with the previously published sequence of prototype HPV16 L1. Some of the mutations changed the triplet codes, subsequently led to changes of amino acids. The mutations of all thirteen HPV16 L1 fragments formed six patterns (XJL1-1 approximately XJL1-6) at nucleic acid level. Compare to HPV16 prototype, their homology were 99.69% to 99.87%. There were four mutations in nucleic acid sequences of XJL1-1, which occurred also in XJL1-2 approximately XJL1-6. Moreover, there are other mutations in XJL1-2 approximately XJL1-6 besides the four mutations in XJ L1-1. The mutations of all thirteen HPV16 L1 fragments formed four patterns at amino acid level, among the mutations XJL1-1/2/3 was by 76.92% (8/13). CONCLUSION: HPV16 type L1 genes from cervical carcinoma biopsies occurred some mutations in Uygur women from southern Xinjiang, and formed several patterns as well as mainstream pattern. The mutations of L1 proteins changed its hydrophobicity and antigenicity. The research suggested that the mutations of HPV16 type L1 genes associated with HPV16 phylogenesis and escape from immune recognition.