Failure to interact with Brd4 alters the ability of HPV16 E2 to regulate host genome expression and cellular movement

•The results describe a role for Brd4 in HPV16 E2 regulation of the host genome.•Highly down regulated genes are not significantly changed but activated genes are.•The results demonstrate that an interaction between HPV16 E2 and Brd4 is involved in co-activating a set of host genes.•Overall the results suggest that the levels of Brd4, or its ability to interact with E2, could determine infection outcome.

The E2 protein of the carcinogen human papillomavirus 16 (HPV16) regulates replication and transcription of the viral genome in association with viral and cellular proteins. Our previous work demonstrated that E2 can regulate transcription from the host genome. E2 can activate transcription from adjacent promoters when located upstream using E2 DNA binding sequences and this activation is dependent upon the cellular protein Brd4; this report demonstrates that a Brd4 binding E2 mutant alters host genome expression differently from wild type E2. Of particular note is that highly down regulated genes are mostly not affected by failure to interact with Brd4 suggesting that the E2-Brd4 interaction is more responsible for the transcriptional activation of host genes rather than repression. Therefore failure to interact efficiently with Brd4, or altered levels of Brd4, would alter the ability of E2 to regulate the host genome and could contribute to determining the outcome of infection.