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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瘤病毒16型(humanpapillomavirus16,HPV16)L2基因的变异,并预测L2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HPV16L2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HPV16L2基因多态性及HPV16L2蛋白功能的变化。结果PCR检测结果显示宫颈癌组织中HPV16L2阳性率为84.21%(1619);测序和序列分析表明L2基因核苷酸多处发生变异,并引起编码氨基酸的变异;L2基因在核苷酸水平上形成7种突变模式(XJL21～XJL27),各模式与HPV16原型比较,同源性在99.37%～99.79%之间;在氨基酸水平上形成5种突变模式,其中XJL1123突变模式占66.67%(812),是突变的主流模式,各模式与HPV16原型比较,同源性在98.31%～99.58%之间;以上突变引起HPV16L2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组织中HPV16L2基因发生多位点变异,并形成多种突变模式和突变主流模式;这些突变引起HPV16L2蛋白疏水性和抗原性的改变,提示HPV16L2基因突变可能与HPV16的系统发生以及病毒逃避机体免疫识别有关。
Objective To investigate the variation of L2 gene of human papillomavirus 16 (HPV16) in Uigur women from southern Xinjiang and to predict the functional changes of L2 protein. Methods DNA was extracted from 19 specimens of uterine cervix cancer biopsy from Uygur women in southern Xinjiang, China. DNA was used as a template to amplify the full-length HPV16L2 gene. PCR products were sequenced directly or cloned and sequenced. Uyghur women with cervical cancer Tissue HPV16L2 gene polymorphism and HPV16L2 protein function changes. Results The positive rate of HPV16L2 in cervical cancer tissues was 84.21% (1619) by PCR. Sequencing and sequence analysis showed that there were multiple nucleotide variations in L2 gene and resulted in variation of the encoded amino acids. L2 gene was formed at nucleotide level Seven kinds of mutation patterns (XJL21 ~ XJL27) showed that the homology was between 99.37% and 99.79% with the HPV16 prototype and five mutations at the amino acid level, of which the mutation pattern of XJL1123 accounted for 66.67% (812) Is the main mode of mutation. Compared with the HPV16 prototype, the patterns of HPV16L2 homology were 98.31% -99.58%. The above mutations caused changes in the hydrophobicity and antigenicity of the HPV16L2 protein, which in turn changed the structure and function of the L1 protein. Conclusion The HPV16L2 gene in cervical cancer tissues of southern Uygur in Xinjiang, China has multi-locus mutation and many kinds of mutation patterns and the main mode of mutation are formed. These mutations cause the change of hydrophobicity and antigenicity of HPV16L2 protein, suggesting that HPV16L2 gene mutation may be associated with Systemic HPV16 and virus escape immune recognition.