The human papillomavirus E7 oncoprotein as a regulator of transcription

•Human papillomavirus E7 both positively and negatively regulates transcription of host cell genes.•E7 regulates factors that control chromatin structure, including histone modifying enzymes and DNA methylation machinery.•E7 modifies the functions of many transcription factor systems, including pRb/E2F, IRFs, SMADs, HIF1, p53, and others.•Transcriptional regulation by E7 impacts host cell proliferation, innate and adaptive immunity, stress responses, differentiation, and DNA damage responses.

High-risk human papillomaviruses (HPVs) encode oncoproteins which manipulate gene expression patterns in the host keratinocytes to facilitate viral replication, regulate viral transcription, and promote immune evasion and persistence. In some cases, oncoprotein-induced changes in host cell behavior can cause progression to cancer, but a complete picture of the functions of the viral oncoproteins in the productive HPV life cycle remains elusive. E7 is the HPV-encoded factor most responsible for maintaining cell cycle competence in differentiating keratinocytes. Through interactions with dozens of host factors, E7 has an enormous impact on host gene expression patterns. In this review, we will examine the role of E7 specifically as a regulator of transcription. We will discuss mechanisms of regulation of cell cycle-related genes by E7 as well as genes involved in immune regulation, growth factor signaling, DNA damage responses, microRNAs, and others pathways. We will also discuss some unanswered questions about how transcriptional regulation by E7 impacts the biology of HPV in both benign and malignant conditions.