The biology of human papillomaviruses: from warts to cancer.
The biology of human papillomaviruses: from warts to cancer.
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人乳头瘤病毒的生物学：从疣到癌症。
DOI：
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发表时间：
1993
期刊：
影响因子：
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通讯作者：
Laimins La
中科院分区：
文献类型：
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作者：
Laimins La
乳头瘤病毒是一种小的DNA病毒，可在大多数哺乳动物（包括人类）中引起各种增生性病变。在已确定的66种人类乳头瘤病毒（hpv）中，包括16、18、31、33和51型的一个子集经常与肛门生殖器癌相关。这些癌症由前体病变发展而来，对于宫颈癌，称为宫颈上皮内瘤变（CIN），并根据上皮分化的破坏程度分为I至III级。病毒产生发生在低级别病变中，这些病变与正常细胞的分化模式只有轻微的改变。病毒颗粒的产生、基因组扩增、衣壳蛋白合成和病毒粒子组装依赖于分化，并且仅限于基上细胞。在癌症中，病毒DNA通常被发现整合到宿主染色体中，没有病毒产生。因此，病毒的转录和复制过程与上皮细胞的分化程序密切相关。过去，由于无法在体外忠实地复制上皮分化程序，对人乳头瘤病毒生命周期的研究受到限制。培养系统的最新进展已经克服了这些问题，允许hpv在体外繁殖。此外，在分子水平上对这些病毒促进恶性肿瘤的机制也有了深入的了解，主要集中在E6和E7病毒癌蛋白的作用上。有证据表明，这些癌蛋白通过使细胞周期调节因子p53和视网膜母细胞瘤失活而起作用，从而为恶性肿瘤的多步骤进展提供了初始事件。
Papillomaviruses are small DNA viruses that induce a variety of proliferative lesions in most mammals, including humans. Of the 66 types of human papillomaviruses (HPVs) that have been identified, a subset that includes types 16, 18, 31, 33, and 51 is associated frequently with anogenital cancers. These cancers develop from precursor lesions, which, for cervical cancer, are termed cervical intraepithelial neoplasias (CIN), and are graded from I to III depending on the degree of disruption of epithelial differentiation. Viral production occurs in low-grade lesions that are only slightly alterated in their pattern of differentiation from normal cells. The production of viral particles, genome amplification, capsid protein synthesis, and virion assembly is dependent upon differentiation and is restricted to suprabasal cells. In carcinomas, viral DNA is usually found integrated into host chromosome, and no viral production is seen. The processes of viral transcription and replication are, therefore, intimately associated with the differentiation program of epithelial cells. In the past, studies on the life cycle of human papillomavirus have been limited due to an inability to faithfully duplicate the epithelial differentiation program in vitro. Recent advances in culture systems, have overcome these problems, allowing for the propagation of HPVs in vitro. In addition, insight has been gained at the molecular level regarding the mechanisms by which these viruses contribute to malignancy, centering on the action of the E6 and E7 viral oncoproteins. Evidence suggests that these oncoproteins function by inactivating the cell cycle regulators p53 and retinoblastoma, thus providing the initial event in a multistep progression to malignancy.