Alp Avcı Gülçin
Gazi University Faculty of Medicine, Department of Medical Microbiology, Ankara, Turkey.
Mikrobiyol Bul. 2012 Jul;46(3):507-15.
Human papillomavirus (HPV) infections are one of the most common sexually-transmitted diseases worldwide. Nowadays, more than 200 HPV types have been identified by DNA sequencing. HPV types are also grouped into three, such as high-risk (types 6, 11, 40, 42, 43, 44, 54, etc), probable high-risk (types 26, 53, 66) and low-risk (types 6, 11, 40, 42, 43, 44, 54, etc) types according to their oncogenic potential. HPV is currently considered as the main aetiological factor of cervical intraepithelial neoplasia and cervical cancer. HPV types classified in Papillomaviridae family, are non-enveloped, icosahedral symmetric viruses about 55 nm in size. Viral genome consists of circular double-stranded DNA, about 8 kb in size, encodes for early proteins (E1, E2, E4, E5, E6, E7) which play role in virus replication and cell transformation, and for late (L1, L2) proteins which are the structural units of the viral capsid. Integration of HPV DNA into the host chromosome is crucial for viral persistence and for carcinogenic effects. Viral DNA may integrate randomly to the cell genome and integration can lead to the deregulation and increase of E6/E7 expression leading to oncogenesis. However, increased expression of E6/E7 gene products may occur without genome integration. E6 and E7 proteins of especially highrisk HPV types (e.g. types 16 and 18) interact with tumor supressor proteins such as p53 and retinoblastoma (pRb) proteins, respectively; inhibit their functions and cause uncontrolled proliferation and immortalization of the cells. The binding of E6 protein to p53 leads its rapid degradation, and the eclipse in the G1 phase, DNA repair mechanisms and apoptosis are terminated. In the other way, E7 protein interacts with pRb and mitotically interactive cellular proteins such as cyclin-E, causing stimulation of cellular DNA synthesis and cell proliferation. Recently identified genes E3 and E8 are located in early gene region and found only in a few papillomavirus types (HPV 1, 11, 16, 31, 33). A fusion protein, E8^E2C, functions as a negative regulator for HPV DNA replication and it is thought that this protein may play a role in the control of viral copy number as well as in the stable maintenance of HPV episomes. In this review article, the genomic structure of HPV and the functions of gene products have been summarized.
人乳头瘤病毒（HPV）感染是全球最常见的性传播疾病之一。如今，通过DNA测序已鉴定出200多种HPV类型。HPV类型也被分为三类，如高危型（6、11、40、42、43、44、54等型）、可能的高危型（26、53、66型）和低危型（6、11、40、42、43、44、54等型），这是根据它们的致癌潜力划分的。HPV目前被认为是宫颈上皮内瘤变和宫颈癌的主要病因。HPV属于乳头瘤病毒科，是无包膜、二十面体对称的病毒，大小约为55纳米。病毒基因组由环状双链DNA组成，大小约为8 kb，编码早期蛋白（E1、E2、E4、E5、E6、E7），这些蛋白在病毒复制和细胞转化中起作用，还编码晚期蛋白（L1、L2），它们是病毒衣壳的结构单位。HPV DNA整合到宿主染色体中对于病毒持续存在和致癌作用至关重要。病毒DNA可能随机整合到细胞基因组中，整合可导致E6/E7表达失调和增加，从而导致肿瘤发生。然而，E6/E7基因产物的表达增加也可能在没有基因组整合的情况下发生。尤其是高危型HPV（如16和18型）的E6和E7蛋白分别与肿瘤抑制蛋白如p53和视网膜母细胞瘤（pRb）蛋白相互作用；抑制它们的功能，导致细胞不受控制的增殖和永生化。E6蛋白与p53的结合导致其快速降解，G1期、DNA修复机制和细胞凋亡终止。另一方面，E7蛋白与pRb以及有丝分裂相互作用的细胞蛋白如细胞周期蛋白E相互作用，刺激细胞DNA合成和细胞增殖。最近鉴定出的E3和E8基因位于早期基因区域，仅在少数乳头瘤病毒类型（HPV 1、11、16、31、33）中发现。一种融合蛋白E8^E2C作为HPV DNA复制的负调节因子，据认为该蛋白可能在控制病毒拷贝数以及HPV游离基因的稳定维持中起作用。在这篇综述文章中，总结了HPV的基因组结构和基因产物的功能。
