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基于E6、E7和L1基因的中国西南地区16型和53型人乳头瘤病毒的遗传变异性和谱系系统发育

Genetic variability and lineage phylogeny of human papillomavirus type-16 and -53 based on the E6, E7, and L1 genes in Southwest China.

作者信息

Cao Man, Chenzhang Yuwei, Ding Xianping, Zhang Yiwen, Jing Yaling, Chen Zuyi

机构信息

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, and Chongqing, China.

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, and Chongqing, China.

出版信息

Gene. 2016 Oct 30;592(1):49-59. doi: 10.1016/j.gene.2016.07.039. Epub 2016 Jul 21.

Abstract

Human papillomaviruses (HPVs) are circular double-stranded DNA viruses that are highly prevalent in the general population, and account for the cervical cancer burden in women worldwide. In this study, we analyzed HPV-16, the most prevalent type worldwide, and HPV-53, a possible high-risk type from infected women in Southwest China. To characterize mutations, intratypic variants, and genetic variability in the E6, E7, and L1 genes of HPV-16 (n=97) and HPV-53 (n=15), these genes were sequenced and submitted to GenBank. Phylogenetic trees were constructed using Bayesian trees, followed by secondary structure analysis and B-cell epitope prediction. Moreover, the selection pressures of the E6, E7, and L1 genes were estimated. In total, 27 novel variants of HPV-16 and 11 novel variants of HPV-53 were identified. In the HPV-16 E6-E7-L1 sequences, 73 nucleotide changes were observed with 40/73 being non-synonymous mutations (two in the alpha helix and five in the beta sheet) and 33/73 being synonymous. In the HPV-53 E6-E7-L1 sequences, 64 nucleotide changes were observed with 26/64 being non-synonymous mutations (three in the alpha helix and one in the beta sheet) and 38/64 being synonymous. Selective pressure analysis showed that most of these mutations did not reflect positive selection. The maximal divergence between any two variants within each gene of these two HPV types ranging from 0.94%(HPV-16 L1 gene)to 2.80%(HPV-53 E6 gene). Identifying new variants of HPV-16 and -53 from women in Southwest China may be helpful to design vaccines specifically for women in Southwest China and testing methods specifically for this region. The results of our study may contribute to future researches in diagnostic probes, vaccines improvement, or screening methods for a particular population.

摘要

人乳头瘤病毒(HPV)是环状双链DNA病毒,在普通人群中高度流行,是全球女性宫颈癌负担的主要原因。在本研究中,我们分析了全球最流行的HPV-16型,以及来自中国西南部感染女性的一种可能的高危型HPV-53。为了表征HPV-16(n=97)和HPV-53(n=15)的E6、E7和L1基因中的突变、型内变异和遗传变异性,对这些基因进行了测序并提交至GenBank。使用贝叶斯树构建系统发育树,随后进行二级结构分析和B细胞表位预测。此外,还估计了E6、E7和L1基因的选择压力。总共鉴定出27种HPV-16新变异和11种HPV-53新变异。在HPV-16 E6-E7-L1序列中,观察到73个核苷酸变化,其中40/73为非同义突变(α螺旋中有两个,β折叠中有五个),33/73为同义突变。在HPV-53 E6-E7-L1序列中,观察到64个核苷酸变化,其中26/64为非同义突变(α螺旋中有三个,β折叠中有一个),38/64为同义突变。选择压力分析表明,这些突变大多未反映正选择。这两种HPV类型各基因内任意两个变异之间的最大差异在0.94%(HPV-16 L1基因)至2.80%(HPV-53 E6基因)之间。鉴定来自中国西南部女性的HPV-16和-53新变异可能有助于设计专门针对中国西南部女性的疫苗以及该地区的检测方法。我们的研究结果可能有助于未来针对特定人群的诊断探针、疫苗改进或筛查方法的研究。

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