The role of the human adenovirus DNA-binding protein DBP in productive and abortive infections.

• Applicant: Professor Dr. Thomas Dobner
• Subject Area: Virology
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 553707811

Adenoviruses (AdVs) are DNA viruses that replicate in the nuclei of infected cells, affecting both humans and animals. They are significant pathogens causing respiratory infections, particularly in children and immunocompromised individuals. While AdVs are generally species-specific, recent studies have shown interspecies transmission between non-human primates and humans. Local outbreaks and the high transmissibility of AdVs highlight their threat to global health, yet there are no specific treatments or widely available vaccines. For over thirty years, AdVs have been used as vectors in gene therapy, cancer therapy, and vaccine development. Their use surged during the COVID-19 pandemic, with many people receiving AdV-based vaccines. AdV infection involves significant reorganization of the host cell nucleus, forming viral replication compartments (RCs). RCs are specialized areas where viral genomes are replicated and expressed, and they play a role in subverting antiviral defenses. Thus, studying RCs is essential for understanding viral replication and virus-host interactions. The human AdV DNA-binding protein (DBP) is a major component of RCs and is crucial for viral DNA replication, transcription, and gene expression. Our recent research showed that DBP is essential for RC assembly and productive viral replication. We identified that a specific amino acid mutation in DBP significantly impacts these processes. AdVs can also cause abortive infections, leading to cell transformation driven by early viral oncogenes E1A and E1B. DBP is also implicated in cell transformation, with mutations in the DBP-encoding gene E2A leading to abortive infections. Since AdV vectors often still contain the E2A gene, understanding the role of DBP during infection is vital, especially for improving the use of these viruses in clinical settings. This proposal aims to clarify the role of DBP in productive and abortive infections. Our findings will also be relevant to other nuclear-replicating DNA viruses due to the functional similarities of their DNA-binding proteins.

• DFG Programme: Research Grants
• Co-Investigator: Dr. Wing Hang Ip