[Genetic regulation of human genital papillomaviruses].
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.
Alvarez-Salas
L M
LM
Laboratory of Biology, National Cancer Institute, National Institutes of Health, Estados Unidos de América.
López-Bayghen
E
E
D003218:Condylomata Acuminata / Q000235:genetics*; D015536:Down-Regulation; D005260:Female; D015967:Gene Expression Regulation, Viral; D005814:Genes, Viral / Q000235:genetics; D005833:Genital Neoplasms, Female / Q000209:etiology; D005834:Genital Neoplasms, Male / Q000209:etiology; D006801:Humans; D008297:Male; D009857:Oncogenes / Q000235:genetics; D027383:Papillomaviridae / Q000235:genetics*; D014158:Transcription, Genetic
Regulación genética de los papilomavirus humanos genitales.