Zhang Yiwen, Cao Man, Wang Mengting, Ding Xianping, Jing Yaling, Chen Zuyi, Ma Tengjiao, Chen Honghan
Key Laboratory of Bio-Resources and Eco-Environment, Ministry of Education; Institute of Medical Genetics, College of Life Science, Sichuan University, China; Bio-resource Research and Utilization Joint Key Laboratory of Sichuan and Chongqing, Sichuan, Chongqing, China.
Gene. 2016 Jul 1;585(1):110-118. doi: 10.1016/j.gene.2016.03.007. Epub 2016 Mar 9.
Human papillomavirus (HPV) is the major causative agent of cervical cancer, which accounts for the second highest cancer burden in women worldwide. HPV-52, the prevalent subtype in Asia, especially in southwest China, was analyzed in this study. To analyze polymorphisms, intratypic variants, and genetic variability in the E6-E7 (n=26) and L1 (n=53) genes of HPV-52, these genes were sequenced and the sequences were submitted to GenBank. Phylogenetic trees were constructed using the neighbor-joining and Kimura 2-parameters methods, followed by analysis of the diversity of secondary structure. Finally, we estimated the selection pressures acting on the E6-E7 and L1 genes. Fifty-one novel variants of HPV-52 L1, and two novel variants of HPV-52 E6-E7 were identified in this study. Thirty single nucleotide changes were observed in HPV-52 E6-E7 sequences with 19/30 non-synonymous mutations and 11/30 synonymous mutations (five in the alpha helix and five in the beta sheet). Fifty-five single nucleotide changes were observed in HPV-52 L1 sequences with 17/55 non-synonymous mutations (seven in the alpha helix and fourteen in the beta sheet) and 38/55 synonymous mutations. Selective pressure analysis predicted that most of these mutations reflect positive selection. Identifying new variants in HPV-52 may inform the rational design of new vaccines specifically for women in southwest China. Knowledge of genetic variation in HPV may be useful as an epidemiologic correlate of cervical cancer risk, or may even provide critical information for developing diagnostic probes.
人乳头瘤病毒(HPV)是宫颈癌的主要致病因子,宫颈癌是全球女性中癌症负担第二高的疾病。本研究分析了HPV-52,它是亚洲尤其是中国西南部的流行亚型。为了分析HPV-52的E6-E7基因(n = 26)和L1基因(n = 53)中的多态性、型内变异和遗传变异性,对这些基因进行了测序,并将序列提交至GenBank。使用邻接法和Kimura双参数法构建系统发育树,随后分析二级结构的多样性。最后,我们估计了作用于E6-E7和L1基因的选择压力。本研究中鉴定出了51个HPV-52 L1的新变异体和2个HPV-52 E6-E7的新变异体。在HPV-52 E6-E7序列中观察到30个单核苷酸变化,其中19/30为非同义突变,11/30为同义突变(5个在α螺旋中,5个在β折叠中)。在HPV-52 L1序列中观察到55个单核苷酸变化,其中17/55为非同义突变(7个在α螺旋中,14个在β折叠中),38/55为同义突变。选择压力分析预测,这些突变大多反映了正选择。鉴定HPV-52中的新变异体可能有助于合理设计专门针对中国西南部女性的新型疫苗。了解HPV的基因变异可能作为宫颈癌风险的流行病学关联有用,甚至可能为开发诊断探针提供关键信息。