The role of BRD4S in the replication cycle of high-risk human papilloma viruses

• Applicant: Professor Dr. Thomas Iftner
• Subject Area: Virology
• Term: since 2020
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 451255034

The papillomavirus E2 protein is a central regulator of viral replication and binds via highly conserved amino acid residues to the cellular BRD4 protein, a multifunctional transcriptional regulator that also plays a role in DNA metabolism. Our preliminary work suggests that only the E2 proteins of carcinogenic high-risk HPV additionally interact with the C-terminal shortened form BRD4S. BRD4S limits transcriptional activation of HPV31 E2 and viral transcription in HPV31-containing cells. This suggests for the first time that BRD4S is a negative regulator of viral transcription and thus possibly contributes to the persistence and pathogenesis of high-risk HPV. In this project the interaction between BRD4S and high-risk HPV E2 proteins will be characterized in detail by in vivo binding studies, functional assays and interactome studies. The aim is to elucidate the exact function of BRD4S in the replication cycle of high-risk HPV. To this end, E2/BRD4S-regulated host cell genes will also be identified. In summary, the project aims to identify new therapeutic structures and approaches for persistent high-risk HPV infections.

• DFG Programme: Research Grants