Project Details
Projekt
Dissecting the fate of Human Adenoviruses (HAdV) in blood and endothelial cells
Applicant
Professorin Anja Ehrhardt, Ph.D.
Subject Area
Virology
Term
since 2026
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 548065690
This project investigates the interaction of human adenoviruses (HAdV) with blood cells and endothelial cells (ECs), aiming to enhance understanding of viral persistence, dissemination, and vector safety. HAdVs are diverse DNA viruses, with 116 identified types grouped into species A–G, varying significantly in tissue tropism, receptor usage, and disease association. While natural infections are typically mild, severe manifestations particularly in immunocompromised individuals can occur. As vectors HAdV provide clinical options in gene therapy, cancer treatment, and vaccination. However, during the COVID-19 pandemic, it became apparent that HAdVs as vector vaccines can also trigger rare adverse effects such as vaccine-induced thrombocytopenia (VITT). However, current knowledge about HAdV in pathogenesis and vector development is largely derived from studies based on a limited number of HAdV types, yet structural and genomic differences between HAdV types suggest potentially distinct type-dependent infection strategies. This project focuses on elucidating how HAdVs interact with blood and endothelial cells (ECs), with the goal of advancing our knowledge of viral persistence, dissemination mechanisms, and the safety of viral vectors. It builds on extensive published and preliminary work, including the development of a recombinant HAdV library (>40 types), advanced genetic tools for viral engineering, and fiber-modified vectors enhancing cell-specific transduction. This project aims to investigate interactions between HAdV and blood cells and ECs based on the complete spectrum of HAdVs. The research will proceed in three work packages. We will (1) analyze the fate of HAdV in blood and ECs. Using wild-type and reporter-tagged HAdVs, the study will quantify viral uptake, replication, cytotoxicity, HAdV DNA persistence and cell activation including both cell lines and primary cells. In a second approach (2) we will explore a directed evolution (ADEVO) approach. Here a peptide-display library will be used to select fiber-modified HAdVs with improved binding and uptake in target cells, such as NK cells. As another goal (3) we plan to vectorize high-efficiency HAdVs by converting them into replication-deficient vectors for testing in different primary 2D and 3D cell models. Note that recombinant viruses will be shared across the research consortium. By mapping HAdV interactions at the cellular level and optimizing vector design, the project seeks to generate safer gene therapy strategies, improve understanding of adenoviral pathogenesis and persistence, and contribute novel tools to the virology research community.
DFG Programme
Research Units
