Role of p300 and WRNIP1 in betapapillomavirus mediated impairment of DNA damage repair

• Applicants: Professor Dr. Baki Akgül, Ph.D.; Dr. Gertrud Steger
• Subject Area: Virology
• Term: since 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 502233329

Human papillomaviruses (HPV) of the genus Beta (betaHPV) are very widespread in the general population and colonize human skin already in the first weeks after birth. BetaHPV are efficiently controlled by the immune system, so that viral replication at very low levels does not lead to clinical manifestations. In immunosuppressed patients, however, there is increased viral replication in the skin. These patients develop non-melanocytic skin tumors (actinic keratoses, squamous cell carcinoma) much more often than the healthy general population. In our preliminary work on human keratinocytes as well as HPV transgenic mice we could show that inhibition of DNA damage repair after UV irradiation by the viral E6 protein is an important mechanism in beta-HPV mediated skin tumorigenesis. The overall goal of this proposal is to further characterize the molecular mechanisms of betaHPV-mediated inhibition of DNA damage repair and to understand the role of the E6 interacting cellular proteins p300 and WRNIP1 (Werner Helicase Interacting Protein 1), which may play different roles during DNA repair. In addition, we aim to develop a novel therapeutic treatment option for betaHPV associated skin tumors using nanobodies targeting the viral proteins E2 and E6.

• DFG Programme: Research Grants