Effects of β-HPV on DNA damage response pathways to drive carcinogenesis: a review

AbstractThe DDR is a complex signaling network responsible for the preservation of genomic integrity. Beta human papillomaviruses ( β-HPVs) are able to destabilize the host genome by attenuating the DDR machinery at the molecular scale following expression of the oncogenes E6 and E7. In the event of β-HPV infection, the E6- and E7-mediated inhibition of the DDR enhances the oncogenicity of UV-induced mutations to enable carcin ogenesis in an otherwise immunocompetent host, marking an important mechanistic divergence from the alpha genus of HPVs. In this review, we summarize recent updates to build upon the ‘hit-and-run’ hypothesis of β-HPV pathomechanism and highlight strain-dependent variations. Simultaneously, we i lluminate points within the β-HPV–DDR interface that may unravel new insights for HPV viral genetics, genus-specific mechanistic models, and developments in targeted molecular therapy of β-HPV-related cancers.
Source: Virus Genes - Category: Genetics & Stem Cells Source Type: research