Project Details
Projekt
Long-term effects of abortive HAdV infection and DNA persistence in cell culture
Applicants
Professor Dr. Thomas Dobner; Dr. Wing Hang Ip
Subject Area
Virology
Term
since 2026
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 548065690
Adenoviruses are widely used as vectors in gene therapy and vaccines due to their high efficiency and the long-standing assumption that they do not integrate into the host genome. However, recent findings challenge this view. Replication-deficient adenoviruses have been shown to integrate into host DNA via non-homologous recombination, potentially disrupting host genes and promoting cellular transformation. Integration can also lead to constitutive expression of viral genes, which may modulate cellular signaling pathways over time. While HAdV-C5 typically integrates only the E1 region, the more oncogenic HAdV-A12 is capable of integrating its entire genome. Moreover, transient expression of regions such as E4 can induce long-lasting cellular changes even in the absence of stable integration. Although integration events are rare, they have been observed both in vitro and in vivo and are influenced by factors such as cell type, vector design, and viral dose. These findings underscore the need for further investigation into the integration and transformation potential of both human and non-human adenoviruses. This project aims to explore how abortive adenovirus infections affect host genome integrity, viral DNA persistence, and cell proliferation. Using mutant human and non-human adenoviruses, we will analyze the effects of infection in primary human cells, focusing on DNA integration and long-term impacts on cell growth. Transformation assays will be conducted to evaluate the oncogenic potential of replication-deficient vectors. By comparing different adenovirus types and vector constructs, we aim to improve risk assessment for adenovirus-based therapies, particularly regarding long-term effects. Our findings will also support the development of safer first- and second-generation vectors. In addition to medical applications, this research will contribute to understanding long-term adenoviral DNA persistence, which may lead to reactivation in immunocompromised patients - especially children - with high mortality rates and no approved treatment options to date.
DFG Programme
Research Units
