Kadaja Meelis, Sumerina Alina, Verst Tatjana, Ojarand Mari, Ustav Ene, Ustav Mart
Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia.
EMBO J. 2007 Apr 18;26(8):2180-91. doi: 10.1038/sj.emboj.7601665. Epub 2007 Mar 29.
Development of invasive cervical cancer upon infection by 'high-risk' human papillomavirus (HPV) in humans is a stepwise process in which some of the initially episomal 'high-risk' type of HPVs (HR-HPVs) integrate randomly into the host cell genome. We show that HPV replication proteins E1 and E2 are capable of inducing overamplification of the genomic locus where HPV origin has been integrated. Clonal analysis of the cells in which the replication from integrated HPV origin was induced showed excision, rearrangement and de novo integration of the HPV containing and flanking cellular sequences. These data suggest that papillomavirus replication machinery is capable of inducing genomic changes of the host cell that may facilitate the formation of the HPV-dependent cancer cell.
人类感染“高危”型人乳头瘤病毒（HPV）后侵袭性宫颈癌的发展是一个逐步的过程，在此过程中，一些最初呈游离状态的“高危”型HPV（HR-HPV）会随机整合到宿主细胞基因组中。我们发现，HPV复制蛋白E1和E2能够诱导HPV起源整合位点的基因组区域发生过度扩增。对诱导整合型HPV起源进行复制的细胞进行克隆分析，结果显示含有HPV的细胞序列以及侧翼细胞序列出现切除、重排和从头整合现象。这些数据表明，乳头瘤病毒复制机制能够诱导宿主细胞发生基因组变化，这可能有助于形成依赖HPV的癌细胞。
