Human Papillomaviruses: Genetic Basis of Carcinogenicity
Human Papillomaviruses: Genetic Basis of Carcinogenicity
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DOI：
10.1159/000214919
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发表时间：
2009-01-01
影响因子：
1.7
通讯作者：
Van Doorslaer, Koenraad
中科院分区：
文献类型：
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作者：
Burk, Robert D.;Chen, Zigui;Van Doorslaer, Koenraad
特定致癌型人乳头瘤病毒（HPV）的持续感染已被确定为宫颈癌的必要病因。HPV基因组之间的DNA序列差异决定了一种HPV是否具有致癌潜力。在基因层面已确定特征的100多种HPV基因型中，至少有15种在不同程度上与宫颈癌相关。基于核苷酸相似性的分类将几乎所有感染宫颈阴道区域的HPV都归入α - PV属。在该属中，从整个病毒基因组推断出的系统发育树将所有致癌类型聚集在一起，这表明致癌型HPV存在一个共同祖先。然而，在由早期开放阅读框（ORF，即E1、E2、E6、E7）或晚期ORF（即L1、L2）构建的不同系统发育树中，致癌潜力与基因组的早期区域相关，而与晚期区域无关。因此，早期区域内的基因差异决定了α - HPV感染的致病潜力。由于HPV基因组是单系的，且整个基因组的位点高度相关，所以使用基因组的任何区域都可以对致癌型和非致癌型进行诊断。在此，我们回顾了我们目前对致癌型HPV进化史的理解，特别是我们关注病毒基因组异质性的重要性，并讨论了部分但并非所有α - PV具有致癌表型的遗传基础。版权所有 (C) 2009 S. Karger AG，巴塞尔
Persistent infection by specific oncogenic human papillomaviruses (HPVs) is established as the necessary cause of cervix cancer. DNA sequence differences between HPV genomes determine whether an HPV has the potential to cause cancer. Of the more than 100 HPV genotypes characterized at the genetic level, at least 15 are associated, to varying degrees, with cervical cancer. Classification based on nucleotide similarity places nearly all HPVs that infect the cervicovaginal area within the alpha-PV genus. Within this genus, phylogenetic trees inferred from the entire viral genome cluster all cancer-causing types together, suggesting the existence of a common ancestor for the oncogenic HPVs. However, in separate trees built from the early open reading frames (ORFs; i.e. E1, E2, E6, E7) or the late ORFs (i.e. L1, L2), the carcinogenic potential sorts with the early region of the genome, but not the late region. Thus, genetic differences within the early region specify the pathogenic potential of alpha-HPV infections. Since the HPV genomes are monophyletic and sites are highly correlated across the genome, diagnosis of oncogenic types and non-oncogenic types can be accomplished using any region across the genome. Here we review our current understanding of the evolutionary history of the oncogenic HPVs, in particular, we focus on the importance of viral genome heterogeneity and discuss the genetic basis for the oncogenic phenotype in some but not all alpha-PVs. Copyright (C) 2009 S. Karger AG, Basel