人乳头瘤病毒 31 型长控制区变异体的功能评估。

Functional evaluation of human papillomavirus type 31 long control region variants.

机构信息

Laboratory of Molecular Studies and Experimental Therapy, Department of Genetics, Federal University of Pernambuco, Brazil.

Department of Virology and Experimental Therapy, Research Center Aggeu Magalhães, Oswaldo Cruz Foundation, Pernambuco, Brazil.

出版信息

Genomics. 2020 Nov;112(6):5066-5071. doi: 10.1016/j.ygeno.2020.09.008. Epub 2020 Sep 6.

DOI:10.1016/j.ygeno.2020.09.008

PMID:32898643

Abstract

Persistent infections by high-risk human papillomavirus (HR-HPV) are a necessary condition, but not sufficient for cervical cancer development. Genetic variants of HR-HPV appear to be related to the risk of persistent infections. The study performed a functional evaluation of variants of the HPV-31 promoter region (LCR). For this, cloning and subcloning of variants HPV-31/UFPE-21 HPV-31/UFPE-89, HPV-31/UFPE-66, E2 gene and prototype HPV-31 were performed. Transfection with different concentrations of E2 was done and the concentration of 25 ng was determined to be ideal for LCR activation. HPV-31/UFPE-21 and HPV-31/UFPE-89 have a greater ability to alter Nluc reporter gene expression levels and HPV-31/UFPE-66 showed decreased levels of gene expression of Nluc reporter gene compared to control. Statistical analysis showed a significant difference between the polymorphic LCR regions and the control (p < 0.0001). A more refined profile of variants of HPV-31 and its importance for the prognosis of cervical lesions begins to be drawn.

摘要

高危型人乳头瘤病毒（HR-HPV）的持续感染是宫颈癌发展的必要条件，但不是充分条件。HR-HPV 的遗传变异似乎与持续性感染的风险有关。本研究对 HPV-31 启动子区域（LCR）的变异进行了功能评估。为此，进行了 HPV-31/UFPE-21、HPV-31/UFPE-89、HPV-31/UFPE-66、E2 基因和原型 HPV-31 的克隆和亚克隆。用不同浓度的 E2 进行转染，确定 25ng 为 LCR 激活的理想浓度。HPV-31/UFPE-21 和 HPV-31/UFPE-89 具有更强的改变 Nluc 报告基因表达水平的能力，而 HPV-31/UFPE-66 与对照相比，Nluc 报告基因的表达水平降低。统计分析显示，多态性 LCR 区与对照之间存在显著差异（p<0.0001）。开始对 HPV-31 的变异体进行更精细的分析，并探讨其对宫颈癌前病变预后的重要性。