Human host factors required for HPV genome transcription

The Human host factors required for HPV genome transcription represent a collective group of cellular proteins hijacked by the Human Papillomavirus (HPV) to facilitate viral gene expression and persistence. A central component of this machinery is Bromodomain-containing protein 4 (BRD4), which is recruited by the viral E2 protein to the Long Control Region (LCR) of the HPV genome (You et al., 2004, Cell) [1]. This interaction is crucial for the recruitment of RNA Polymerase II and the Mediator complex, driving the transcription of early oncogenes E6 and E7 (Wu et al., 2013, Genes & Development) [2]. Additionally, ubiquitous host transcription factors such as AP-1, Sp1, and NF-1 bind to specific motifs within the LCR to regulate promoter activity and viral load (Gloss et al., 1987, EMBO J) [3]. Therapeutically, this group of factors is targeted primarily through the use of BET inhibitors, such as JQ1 and Birabresib, which disrupt the binding of BRD4 to acetylated histones and the viral E2 protein (Smith et al., 2016, Antiviral Research) [4]. While these agents show promise in reducing viral oncogene expression and inducing growth arrest in HPV-associated cancers, they face challenges regarding systemic toxicity due to the essential role of these host factors in normal cellular transcription (Piha-Paul et al., 2019, Lancet Oncology) [5]. Monitoring the levels of E6/E7 mRNA and the stabilization of p53 and pRb proteins serves as a primary method for assessing the efficacy of drugs targeting these host factors [4][6].

Other names

HPV transcription host machineryHost cell factors for HPV E2HPV-host transcriptional interactomeHPV-host cell interactome

Inhibition of BET bromodomain binding to acetylated lysines, disruption of the E2-BRD4 interaction, and suppression of RNA polymerase II-mediated viral transcription.