Elucidating the mechanisms of host cell gene expression control by human papillomavirus (HPV) (360G-Wellcome-211972_Z_18_Z)

The Parish lab has demonstrated that the cellular protein CCCTC-binding factor (CTCF) associates with several sites within HPV genomes. The known cellular functions of CTCF include transcription insulation, epigenetic boundary formation and genetic imprinting, but why CTCF is specifically recruited to HPV genomes has not yet been established. The association of CTCF with its cellular target sequences changes upon cellular differentiation and this affects gene expression. ChIP-Seq experiments performed in the lab show that HPV infection results in a rapid and stable re-distribution of CTCF throughout the host cell genome. In addition, gene expression array analysis of HPV negative and HPV positive cells shows that expression of many genes is altered upon HPV infection. For example, CTCF recruitment to the cellular L3MBTL4 locus is significantly reduced following HPV infection, corresponding to a dramatic decrease in the expression of L3MBTL4 transcript encoding a methyltransferase thought to be important for the methylation of histones. The alteration of L3MBTL4 expression in this manner allows HPV to dramatically alter the cellular environment to support viral persistence. We hypothesise that HPV infection deregulates CTCF-dependent control of specific loci to facilitate efficient life cycle completion and maintain persistent infection.