APOBEC3B regulates HPV replication by inducing R-loop formation and genomic instability [RNA-Seq]

Reduction of R-loop levels through overexpression of the R-loop specific RNase, RNase H1, impaired A3B binding to viral genomes as well as at multiple cellular sites. When A3B was depleted, total R-loop levels decreased by ~50%, leading to impaired viral transcription and an increase in the expression of immune genes, such as OASL, IL6, and IRF1. Mapping R-loop formation in A3B depleted cells revealed that A3B regulated a subset of R-loops that form on the transcriptional start (TSS) and termination sites (TTS) of cellular genes, including at the HPV URR.

Furthermore, A3B depletion resulted in over a 50% reduction of DNA breaks along with altered expression of DNA damage repair proteins. This study demonstrates that A3B is an inducer of R-loop formation and genomic instability in HPV positive cells, thereby regulating cellular and viral gene expression along with HPV replication.