Beta HPV Deregulates Double-Strand Break Repair

Abstract

Beta human papillomavirus (beta HPV) infections are common in adults. Certain types of beta HPVs are associated with nonmelanoma skin cancer (NMSC) in immunocompromised individuals. However, whether beta HPV infections promote NMSC in the immunocompetent population is unclear. They have been hypothesized to increase genomic instability stemming from ultraviolet light exposure by disrupting DNA damage responses. Implicit in this hypothesis is that the virus encodes one or more proteins that impair DNA repair signaling. Fluorescence-based reporters, next-generation sequencing, and animal models have been used to test this primarily in cells expressing beta HPV E6/E7. Of the two, beta HPV E6 appears to have the greatest ability to increase UV mutagenesis, by attenuating two major double-strand break (DSB) repair pathways, homologous recombination, and non-homologous end-joining. Here, we review this dysregulation of DSB repair and emerging approaches that can be used to further these efforts.