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希腊女性宫颈病变中人乳头瘤病毒 16 型 E2 基因的序列变异分析。

Sequence variation analysis of the E2 gene of human papilloma virus type 16 in cervical lesions from women in Greece.

机构信息

Microbiology-Virology Laboratory, Department of Biochemistry and Biotechnology, School of Health Sciences, University of Thessaly, Ploutonos 26 and Aiolou, 41221 Larissa, Greece.

出版信息

Arch Virol. 2012 May;157(5):825-32. doi: 10.1007/s00705-012-1236-8.

Abstract

The E2 gene of human papilloma virus is expressed at the early stage of the viral life cycle, encoding the E2 transcription factor, and regulates the expression of E6 and E7 oncogenes. Disruption of E2 gene due to viral integration inhibits the transcriptional suppression of the HPV oncogenes, inducing cell proliferation. In the present study, a total of 22 HPV16-positive cytological specimens derived from high- and low-grade cervical intraepithelial lesions were investigated in order to identify sequence variations in the HPV16 E2 ORF. The E2 gene was amplified by PCR using external and internal overlapping sets of primers. Amplicons were cloned and sequenced. Disruption sites were detected in cervical samples diagnosed as high-grade cervical intraepithelial lesions. Moreover, sequence variations were identified in the E2 ORF and specific variations were associated with non-European variants such as African type I, African type II and Asian American. A total of three new sequence variations were identified at positions 2791, 2823 (transactivation domain) and 3361 (hinge region). Distinct phylogenetic branches were formed according to E2 analysis that characterized the different HPV16 variants. It was ascertained that non-European variants are circulating in the Greek population.

摘要

人乳头瘤病毒(HPV)E2 基因在病毒生命周期的早期表达,编码 E2 转录因子,并调节 E6 和 E7 癌基因的表达。由于病毒整合导致 E2 基因缺失,抑制了 HPV 癌基因的转录抑制,从而诱导细胞增殖。在本研究中,共检测了 22 例 HPV16 阳性细胞学标本,这些标本来自高级别和低级别宫颈上皮内病变,以鉴定 HPV16 E2 ORF 中的序列变异。使用外部和内部重叠引物的 PCR 扩增 E2 基因。扩增子被克隆和测序。在诊断为高级别宫颈上皮内病变的宫颈样本中检测到破坏位点。此外,还在 E2 ORF 中鉴定出序列变异,并且特定的变异与非欧洲变体如非洲 I 型、非洲 II 型和亚裔美国人有关。在位置 2791、2823(转录激活域)和 3361(铰链区)处共鉴定出三种新的序列变异。根据 E2 分析形成了不同的进化枝,这些进化枝特征化了不同的 HPV16 变体。确定了非欧洲变体在希腊人群中流行。

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