Papillomavirus infections--a major cause of human cancers.
Papillomavirus infections--a major cause of human cancers.
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DOI：
10.1002/9783527609314.ch5
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发表时间：
1996
期刊：
影响因子：
--
通讯作者：
H. zur Hausen
中科院分区：
文献类型：
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作者：
H. zur Hausen
乳头瘤病毒家族代表了一组异质的病毒。目前，已在人类中鉴定出77种不同的基因型，并从30多种假定的新基因型中获得了部分序列。个体基因型的碱基组成的地理差异通常很小，这表明突变率很低，因此今天的原型的起源很古老。基因组相对较小的尺寸允许分析单个基因功能和病毒蛋白与宿主细胞成分的相互作用。增殖细胞包含潜伏形式的病毒基因组，大规模的病毒DNA复制，以及后期病毒蛋白的翻译和功能活性，病毒颗粒组装仅限于分化皮肤和粘膜层。在人类中，乳头瘤病毒感染引起各种良性增生：疣、上皮囊肿、上皮内瘤变、肛门生殖器、口喉和咽乳头瘤、角棘瘤和其他类型的角化过度。它们在一些主要人类癌症的病因学中的作用特别令人感兴趣：特定类型（HPV 16、18和其他几种）已被确定为至少90%的子宫颈癌的病原体，也与50%以上的其他肛门生殖器癌症有关。这些HPV类型被认为是“高风险”感染。它们的E6/E7癌蛋白通过激活细胞周期蛋白E和A来刺激细胞增殖，并干扰细胞蛋白RB和p53的功能。后一种相互作用似乎是它们的致突变性和非整倍性活性的原因，这是这些含有HPV的病变进展和高风险HPV类型作为孤立致癌物的作用的潜在原理。在未转化的人角质形成细胞中，病毒癌蛋白的转录和功能受细胞间和细胞内信号级联控制，它们的中断是永生和恶性生长的先决条件。最近，在高比例的非黑色素瘤皮肤癌（基底细胞癌和鳞状细胞癌）中也发现了新的和已知的HPV类型。与一种罕见的遗传性疾病——疣状表皮发育不良（以广泛的疣状病变和皮肤癌为特征）患者的观察结果相似，基底细胞癌和鳞状细胞癌优先发生在光照部位。这可能表明物理致癌物（阳光的紫外线部分）与“低风险”（非诱变）乳头瘤病毒感染之间存在相互作用。关于在口腔癌、喉癌和食道癌中存在HPV感染的报道进一步强调了这一病毒群作为已证实和怀疑的人类致癌物的重要性。
The papillomavirus family represents a remarkably heterogeneous group of viruses. At present, 77 distinct genotypes have been identified in humans and partial sequences have been obtained from more than 30 putative novel genotypes. Geographic differences in base composition of individual genotypes are generally small and suggest a low mutation rate and thus an ancient origin of today's prototypes. The relatively small size of the genome permitted an analysis of individual gene functions and of interactions of viral proteins with host cell components. Proliferating cells contain the viral genome in a latent form, large scale viral DNA replication, as well as translation and functional activity of late viral proteins, and viral particle assembly are restricted to differentiating layers of skin and mucosa. In humans papillomavirus infections cause a variety of benign proliferations: warts, epithelial cysts, intraepithelial neoplasias, anogenital, oro-laryngeal and -pharyngeal papillomas, keratoacanthomas and other types of hyperkeratoses. Their involvement in the etiology of some major human cancers is of particular interest: specific types (HPV 16, 18 and several others) have been identified as causative agents of at least 90% of cancers of the cervix and are also linked to more than 50% of other anogenital cancers. These HPV types are considered as 'high risk' infections. Their E6/E7 oncoproteins stimulate cell proliferation by activating cyclins E and A, and interfere with the functions of the cellular proteins RB and p53. The latter interaction appears to be responsible for their mutagenic and aneuploidizing activity as an underlying principle for the progression of these HPV-containing lesions and the role of high risk HPV types as solitary carcinogens. In non-transformed human keratinocytes transcription and function of viral oncoproteins is controlled by intercellular and intracellular signalling cascades, their interruption emerges as a precondition for immortalization and malignant growth. Recently, novel and known HPV types have also been identified in a high percentage of non-melanoma skin cancers (basal and squamous cell carcinomas). Similar to observations in patients with a rare hereditary condition, epidermodysplasia verruciformis, characterized by an extensive verrucosis and development of skin cancer, basal and squamous cell carcinomas develop preferentially in light-exposed sites. This could suggest an interaction between a physical carcinogen (UV-part of the sunlight) and a 'low risk' (non-mutagenic) papillomavirus infection. Reports on the presence of HPV infections in cancers of the oral cavity, the larynx, and the esophagus further emphasize the importance of this virus group as proven and suspected human carcinogens.