The biological properties of E6 and E7 oncoproteins from human papillomaviruses

Abstract

More than 100 different human papillomavirus (HPV) types have been isolated so far, and they can be sub-grouped in cutaneous or mucosal according to their ability to infect the skin or the mucosa of the genital or upper-respiratory tracts. A sub-group of human mucosal HPVs, referred to as high-risk HPV types, is responsible for approximately 5% of all human cancers, which represents one-third of all the tumours induced by viruses. Epidemiological and biological studies have shown that HPV16 is the most oncogenic type within the high-risk group. Emerging lines of evidence suggest that, in addition to the high-risk mucosal HPV types, certain cutaneous HPVs are involved in skin cancer. HPV-associated cancers are intimately linked to HPV persistence and the accumulation of chromosomal rearrangements. The products of the early genes, E6 and E7, of the high-risk mucosal HPV types play a key role in both events. Indeed, these proteins have developed a number of strategies to evade host immuno-surveillance allowing viral persistence, and to alter cell cycle and apoptosis control, facilitating the accumulation of DNA damage/mutations. Often, the two oncoproteins target the same cellular pathways with different mechanisms, showing a strong synergism in promoting cellular transformation and neutralizing the immune response. Here, we review most of the findings on the biological properties and molecular mechanisms of the oncoproteins E6 and E7 from mucosal and cutaneous HPV types.

Biology of Human Papillomavirus Infections in Head and Neck Carcinogenesis

“…HPVs critically depend on the cellular machinery for the replication of their genome [3,5]. During the course of infection in proliferating basal cells or in transformed cell systems, HPVs establish their genomes as low-copy-number, autonomously replicating episomes [3,5,19,20]. HPV DNA replicates during the S phase, in synchrony with the host cell chromosome, and the mechanism of initiation of replication is fundamentally the same as that of eukaryotic chromosomes [19].…”

“…3. E2 is also capable of binding to the mitotic chromatin by cellular protein Brd 4, aiding in segregation of viral DNA to the daughter cells during cell division [3,19].…”

“…E1 interacts with several cellular genes to synchronize the viral replication to host cell replication and is critical for G1/S transition and S phase. E1 also has an important role in retaining the episomal state of the viral molecule, i.e., keeping it separate from the host cell chromosome [3,5,19,20].…”

“…Hence, the HPVs, especially viral proteins E5, E6 and E7, have developed strategies to subvert cellular growth regulatory pathways and are able to uncouple cellular proliferation and differentiation [3,5,19,20]. E7 is the most important driver of the cell cycle deregulation (Fig.…”

Transcriptional regulation of genes involved in keratinocyte differentiation by human papillomavirus 16 oncoproteins

“…The E6 and E7 early gene products are responsible for the oncogenic potential of high-risk HPVs [ 2 ]. The transforming activity of E6 and E7 is mainly mediated through the inactivation of cellular tumour suppressor proteins.…”