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乌拉圭女性宫颈样本中人类乳头瘤病毒16型E6、E7基因及长控制区的分析

Analysis of human papillomavirus 16 E6, E7 genes and Long Control Region in cervical samples from Uruguayan women.

作者信息

Ramas Viviana, Mirazo Santiago, Bonilla Sylvia, Ruchansky Dora, Arbiza Juan

机构信息

Sección Virología, Facultad de Ciencias, Universidad de la República, Iguá 4225, 11400 Montevideo, Uruguay.

Laboratorio de Citología, Servicio de Atención a la Salud, Intendencia Municipal de Montevideo, Martín C. Martínez 1677, 11200 Montevideo, Uruguay.

出版信息

Gene. 2018 May 15;654:103-109. doi: 10.1016/j.gene.2018.02.023. Epub 2018 Feb 14.

Abstract

OBJECTIVE

This study aims to investigate the HPV16 variant distribution by sequence analyses of E6, E7 oncogenes and the Long Control Region (LCR), from cervical cells collected from Uruguayan women, and to reconstruct the phylogenetic relationships among variants.

METHODS

Forty-seven HPV16 variants, obtained from women with HSIL, LSIL, ASCUS and NILM cytological classes were analyzed for LCR and 12 were further studied for E6 and E7. Detailed sequence comparison, genetic heterogeneity analyses and phylogenetic reconstruction were performed.

RESULTS

A high variability was observed among LCR sequences, which were distributed in 18 different variants. E6 and E7 sequences exhibited novel non-synonymous substitutions. Uruguayan sequences mainly belonged to the European lineage, and only 5 sequences clustered in non-European branches; 3 of them in the Asian-American and North-American linage and 2 in an African branch. Additionally, 6 new variants from European and African clusters were identified.

CONCLUSIONS

HPV16 isolates mainly belonged to the European lineage, though strains from African and Asian-American lineages were also identified. Herein is reported for the first time the distribution and molecular characterization of HPV16 variants from Uruguay, providing novel insights on the molecular epidemiology of this infectious disease in the South America.

SYNOPSIS

A high variability among HPV 16 isolates mainly belonged to European lineage, provides an extensive sequence dataset from a country with high burden of cervical cancer.

摘要

目的

本研究旨在通过对从乌拉圭女性宫颈细胞中收集的E6、E7致癌基因和长控制区(LCR)进行序列分析,调查HPV16变体的分布情况,并重建变体之间的系统发育关系。

方法

对从患有高度鳞状上皮内病变(HSIL)、低度鳞状上皮内病变(LSIL)、非典型鳞状细胞不能明确意义(ASCUS)和未见上皮内病变或恶性病变(NILM)细胞学分类的女性中获得的47个HPV16变体进行LCR分析,并对其中12个进一步进行E6和E7研究。进行了详细的序列比较、遗传异质性分析和系统发育重建。

结果

在LCR序列中观察到高度变异性,其分布在18种不同的变体中。E6和E7序列表现出新的非同义替换。乌拉圭序列主要属于欧洲谱系,只有5个序列聚集在非欧洲分支中;其中3个在亚美和北美谱系中,2个在非洲分支中。此外,还鉴定出6个来自欧洲和非洲簇的新变体。

结论

HPV16分离株主要属于欧洲谱系,不过也鉴定出了来自非洲和亚美谱系的菌株。本文首次报道了乌拉圭HPV16变体的分布和分子特征,为南美洲这种传染病的分子流行病学提供了新的见解。

概要

HPV 16分离株之间的高度变异性主要属于欧洲谱系,提供了来自宫颈癌负担较高国家的广泛序列数据集。

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