Lehoux Michaël, D'Abramo Claudia M, Archambault Jacques
Laboratory of Molecular Virology, Institut de Recherches Cliniques de Montréal, Montreal, Que., H2W 1R7 Canada.
Public Health Genomics. 2009;12(5-6):268-80. doi: 10.1159/000214918. Epub 2009 Aug 11.
Approximately 20% of all cancers are associated with infectious agents. Among them, human papillomaviruses (HPVs) are very common and are now recognized as the etiological agent of cervical cancer, the second most common cancer in women worldwide, and they are increasingly linked with other forms of dysplasia. Carcinogenesis is a complex and multistep process requiring the acquisition of several genetic and/or epigenetic alterations. HPV-induced neoplasia, however, is in part mediated by the intrinsic functions of the viral proteins. In order to replicate its genome, HPV modulates the cell cycle, while deploying mechanisms to escape the host immune response, cellular senescence and apoptosis. As such, HPV infection leads directly and indirectly to genomic instability, further favouring transforming genetic events and progression to malignancy. This review aims to summarize our current understanding of the molecular mechanisms exploited by HPV to induce neoplasia, with an emphasis on the role of the 2 viral oncoproteins E6 and E7. Greater understanding of the role of HPV proteins in these processes will ultimately aid in the development of antiviral therapies, as well as unravel general mechanisms of oncogenesis.
大约20%的癌症与感染因子有关。其中，人乳头瘤病毒（HPV）非常常见，现在被认为是宫颈癌的病因，宫颈癌是全球女性中第二常见的癌症，并且它们与其他形式的发育异常的联系日益增加。致癌作用是一个复杂的多步骤过程，需要获得多种遗传和/或表观遗传改变。然而，HPV诱导的肿瘤形成部分是由病毒蛋白的内在功能介导的。为了复制其基因组，HPV调节细胞周期，同时部署机制以逃避宿主免疫反应、细胞衰老和凋亡。因此，HPV感染直接和间接导致基因组不稳定，进一步促进转化性遗传事件和向恶性肿瘤的进展。本综述旨在总结我们目前对HPV诱导肿瘤形成所利用的分子机制的理解，重点是两种病毒癌蛋白E6和E7的作用。对HPV蛋白在这些过程中的作用有更深入的了解最终将有助于开发抗病毒疗法，并揭示肿瘤发生的一般机制。
