Alvarez-Salas L M, López-Bayghen E
Laboratory of Biology, National Cancer Institute, National Institutes of Health, Estados Unidos de América.
Salud Publica Mex. 1995 May-Jun;37(3):241-7.
Human papillomavirus (HPV) specifically infect stratified epithelial cells, causing benign and malignant neoplasia. Several elements directing this virus' genetic expression are present in a non-coding region called LCR. HPV infection starts in the basal cells of stratified epithelia, where a particular combination of cellular factors interacting with the LCR starts the transcription of the viral E6 and E7 oncogenes. The E6 and E7 genes alter the cell cycle because they interact and inactivate tumor suppressor proteins: E6 binds and degrades protein p53 and E7 associates with p105RB. E1 and E2 are the next synthesized proteins. E2 blocks the early transcription and permits E1 specific binding to the viral origin of replication located within the LCR, initiating the viral genome replication. Following the course of viral infection, the E2-induced E6 and E7 down-regulation releases p53 and p105RB proteins, and the differentiation process can continue. Then, a putative late promoter can activate the capsid genes L1 and L2. At this step, mature virions can be detected in the upper layers of the epithelium. Disruption in E2 gene transcription is usually associated to genital malignant neoplasia. In the absence of E2, E6 and E7 remain constitutively expressed, sustaining the immortality of the infected cell and blocking the epithelial differentiation program.
人乳头瘤病毒（HPV）特异性感染复层上皮细胞，可导致良性和恶性肿瘤形成。指导该病毒基因表达的几个元件存在于一个称为长控制区（LCR）的非编码区域中。HPV感染始于复层上皮的基底细胞，在那里，与LCR相互作用的特定细胞因子组合启动病毒E6和E7癌基因的转录。E6和E7基因改变细胞周期，因为它们相互作用并使肿瘤抑制蛋白失活：E6结合并降解蛋白p53，E7与p105RB结合。E1和E2是接下来合成的蛋白质。E2阻断早期转录，并允许E1特异性结合位于LCR内的病毒复制起点，启动病毒基因组复制。在病毒感染过程中，E2诱导的E6和E7下调释放p53和p105RB蛋白，分化过程得以继续。然后，一个假定的晚期启动子可以激活衣壳基因L1和L2。在这一步，可以在上皮的上层检测到成熟的病毒颗粒。E2基因转录的破坏通常与生殖器恶性肿瘤有关。在没有E2的情况下，E6和E7持续表达，维持被感染细胞的永生并阻断上皮分化程序。
