中国中部地区人乳头瘤病毒 16 型 E6 和 E7 基因的遗传变异。

Genetic variation of E6 and E7 genes of human papillomavirus type 16 from central China.

机构信息

Department of Laboratory Medicine, Jingzhou Hospital Affiliated to Yangtze University, Jingzhou, 434020, China.

出版信息

Virol J. 2023 Sep 27;20(1):217. doi: 10.1186/s12985-023-02188-8.

DOI:10.1186/s12985-023-02188-8

PMID:37759219

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10537582/

Abstract

BACKGROUND

Persistent high-risk human papillomavirus (HR-HPV) infection is an important factor in the development of cervical cancer, and human papillomavirus type 16 (HPV-16) is the most common HR-HPV type worldwide. The oncogenic potential of HPV-16 is closely related to viral sequence variation.

METHODS

In order to clarify the variant characteristics of HPV-16 E6 and E7 genes in central China, E6 and E7 sequences of 205 HPV-16 positive samples were amplified by polymerase chain reaction. PCR products of E6 and E7 genes were further sequenced and subjected to variation analysis, phylogenetic analysis, selective pressure analysis and B-cell epitope prediction.

RESULTS

Twenty-six single nucleotide variants were observed in E6 sequence, including 21 non-synonymous and 5 synonymous variants. Twelve single nucleotide variants were identified in E7 sequence, including 6 non-synonymous and 6 synonymous variants. Four new variants were found. Furthermore, nucleotide variation A647G (N29S) in E7 was significantly related to the higher risk of HSIL and cervical cancer. Phylogenetic analysis showed that the E6 and E7 sequences were all distributed in A lineage. No positively selected site was found in HPV-16 E6 and E7 sequences. Non-conservative substitutions in E6, H31Y, D32N, D32E, I34M, L35V, E36Q, L45P, N65S and K75T, affected multiple B-cell epitopes. However, the variation of E7 gene had little impact on the corresponding B-cell epitopes (score < 0.85).

CONCLUSION

HPV-16 E6 and E7 sequences variation data may contribute to HR-HPV prevention and vaccine development in Jingzhou, central China.

摘要

背景

持续性高危型人乳头瘤病毒（HR-HPV）感染是宫颈癌发展的重要因素，而 HPV-16 是人乳头瘤病毒中最常见的 HR-HPV 类型。HPV-16 的致癌潜能与其病毒序列变异密切相关。

方法

为了阐明 HPV-16 E6 和 E7 基因在中国中部地区的变异特征，采用聚合酶链反应（PCR）扩增了 205 例 HPV-16 阳性样本的 E6 和 E7 序列。进一步对 E6 和 E7 基因的 PCR 产物进行测序，并进行变异分析、系统发育分析、选择压力分析和 B 细胞表位预测。

结果

在 E6 序列中观察到 26 个单核苷酸变异，包括 21 个非同义变异和 5 个同义变异。在 E7 序列中发现 12 个单核苷酸变异，包括 6 个非同义变异和 6 个同义变异。还发现了 4 个新的变异。此外，E7 中的核苷酸变异 A647G（N29S）与 HSIL 和宫颈癌的高风险显著相关。系统发育分析显示，E6 和 E7 序列均分布在 A 谱系中。在 HPV-16 E6 和 E7 序列中未发现阳性选择位点。E6 中的非保守性替换，包括 H31Y、D32N、D32E、I34M、L35V、E36Q、L45P、N65S 和 K75T，影响了多个 B 细胞表位。然而，E7 基因的变异对相应的 B 细胞表位影响较小（评分<0.85）。