Project Details
Projekt
Comparative analysis of human adenovirus immune evasion
Applicants
Dr. Anne Halenius; Dr. Zsolt Ruzsics
Subject Area
Virology
Term
since 2026
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 548065690
In immunocompetent individuals, the human immune system can effectively prevent systemic infections with human adenoviruses (HAdVs), while in immunocompromised patients HAdV infections may become systemic and life-threatening. Hence, to overcome immune control HAdVs employ a variety of sophisticated strategies encoded in the E3 region that promote their survival and spread within and between hosts. Adenoviruses are also frequently used as vectors in vaccines and oncolytic therapies. Oncolytic vectors often rely on replication-competent adenoviruses with partial or complete deletions in the E3 region, which encode immune evasion functions. Recent findings suggest that selected elements of this region can enhance the therapeutic efficacy of such vectors. Nevertheless, current knowledge of how the E3 region of different HAdVs influences antigen presentation and immune recognition is still limited. The aim of this project is to elucidate the immune evasion mechanisms encoded by the E3 region of HAdVs and to investigate how variations across HAdVs and vector types affect recognition by the immune system. By analyzing a panel of wild-type and E3-deleted viruses, we aim to uncover both conserved and species-specific strategies that influence susceptibility to cytotoxic T lymphocyte (CTL) and natural killer (NK) cell responses. Particular emphasis will be placed on understanding how E3 genes affect HLA class I-mediated antigen presentation, providing a detailed view of the adenovirus-specific HLA-I ligandome. We will also examine how different vector backbones impact CTL and NK cell recognition. Finally, we will explore the role of TRIM21, a cytosolic antibody receptor, in enhancing antigen presentation from incoming viral particles in the context of pre-existing immunity. This project is expected to generate detailed molecular insights into how E3-encoded functions modulate immune detection, uncover novel adenovirus-derived HLA-I ligands, and identify key viral and host determinants that shape T and NK cell responses. These findings can be applied for the design of adenoviral vectors with optimized immunogenicity and therapeutic efficacy. Moreover, the comprehensive HLA-I ligandome analysis will yield candidate epitopes with potential applications in the development of targeted T-cell immunotherapies.
DFG Programme
Research Units
