The Biology of Human Papillomaviruses
The Biology of Human Papillomaviruses
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DOI：
10.1159/000355959
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发表时间：
2014-01-01
期刊：
影响因子：
--
通讯作者：
Rady, Peter L.
中科院分区：
文献类型：
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作者：
Nguyen, Harrison P.;Ramirez-Fort, Marigdalia K.;Rady, Peter L.
人乳头瘤病毒(HPV)是一种小的双链DNA病毒，会在皮肤和粘膜组织中造成损害，并导致宫颈癌、阴道癌、外阴癌和阴茎癌。人类乳头状瘤病毒分为5个属，总共约有150个物种已被测序。其基因组由编码病毒调节蛋白的早期(E)区、编码病毒结构蛋白的晚期(L)区和对病毒生命周期至关重要的非编码区组成。要发生感染，病毒必须进入基底层表皮，在那里，在内吞和病毒衣壳分解之后，L2蛋白介导病毒基因组转移到有丝分裂角质形成细胞的核。病毒基因组在正常生命周期中以异体形式存在，并在E1、E2、E4和E5病毒蛋白的介导下与宿主细胞DNA同步复制。然而，在大多数高级别宫颈肿瘤中，病毒DNA通过破坏E2开放阅读框架整合到宿主基因组中。之前被E2抑制的癌蛋白E6和E7随后可以自由地抑制Rb和P53肿瘤抑制途径。病毒的生命周期结束于病毒基因组的包装和病毒的释放，这需要E2介导的L2到复制区的募集，L1的表达和二十面体衣壳在细胞核中的组装。总体而言，HPV的复杂生物学仍然是一个重要的研究领域，对公共卫生具有重大影响。(C)2014年S.Karger AG，巴塞尔
Human papillomaviruses (HPVs) are small, double-stranded DNA viruses that cause lesions in cutaneous and mucosal tissue and are responsible for carcinomas of the cervix, vagina, vulva and penis. HPVs sort into 5 genera with a total of approximately 150 species that have been sequenced. Its genome is comprised of an early (E) region encoding the viral regulatory proteins, a late (L) region encoding the viral structural proteins and a noncoding region that is essential to the viral life cycle. For infection to occur, the virus must access the basal epidermal layer where, following endocytosis and viral capsid disassembly, the L2 protein mediates viral genome transfer to the nuclei of mitotic keratinocytes. The viral genome is maintained in episomal form during the normal life cycle and replicates in synchrony with the host cell DNA under the mediation of E1, E2, E4 and E5 viral proteins. In most high-grade cervical neoplasms, however, the viral DNA is integrated into the host genome through the disruption of the E2 open reading frame. The oncoproteins E6 and E7, which were previously suppressed by E2, are then free to inhibit the Rb and p53 tumor suppressor pathways. The viral life cycle concludes with the packaging of the viral genome and virus release, which entails the E2-mediated recruitment of L2 to regions of replication, the expression of L1 and the assembly of the icosahedral capsid in the nucleus. Overall, the complex biology of HPV continues to be an important area of research with substantial implications for public health. (c) 2014 S. Karger AG, Basel