Prokaryotic Expression, Vector Construction Of Different Promoters And Animal Model Study Of HPV-16 E6/E7 Gene

Human papillomaviruses (HPVs) are double-stranded covalently closed circular DNA (cccDNA) viruses, and the productive phase of the viral life cycle elaborated in the upper squamous epithelial cell layers. To date, there are more than 100 types of HPVs, but only a subset of"high-risk"viral types induced cerviral carcinogenesis. High-risk HPVs, such as HPV-16, 18, 31, have been directly linked to genital infection that can progress to malignancy. They integrate their genomes into the chromosome of the host cell to induce immortalization and transformation. In contrast, low-risk HPV types, which also infect genital epithelia, primarily induce benign lesions, e.g. condyloma acuminatum.HPVs coded two genes in their early region, E6 and E7, and high-risk viral types encode E6 and E7 oncoproteins with an enhanced affinity for host cellular targets.Whereas transcriptional activity has been associated with both E6 and E7, the major thrust of investigation has centered on protein-protein interactions with cellular targets. E6 degradated p53 protein via the ubiquitin pathway. Thus, impairing the ability of cells to either arrest the cell cycle or enter the apoptotic pathway in response to DNA damage. E7 binded, destabilized, and consequently destructed pRB,p107,and p130. At the same time ,it sequestrated Mi2 histone deacetylase,inducted c-Myc to abrogate transforming growth factorβinhibitory signaling.