Incompletely defined initial steps of transcription and temporal silencing are decisive in the establishment of productive or persistent HAdV infections with potential reactivation events later that cause death in the absence of protective immunity. With the data obtained in the first funding period we plan a collaborative comprehensive approach to unravel the interactions between HAdV types and host cell defenses. We will also elaborate on the precise mechanism behind the early-to-late switch and analyze viral chromatin accessibility and repressor occupancy in dependency of our hit candidates that we identified in a genome-wide manner to understand the hidden switches between silencing and activation of early versus late viral gene expression. Our focus will now also extend to how these mechanisms differ among non-C-type HAdV (species A-G) that impede different entry routes and manifestations, enabling insights into how different viral species may employ distinct strategies for gene regulation and immune evasion. Ultimately, this planned project seeks to contribute to a comprehensive understanding of productive infection, reactivation leading to the development of innovative strategies for therapeutic purposes in a collaborative manner with other DEEP-DV members.

To answer these questions we are applying multiple tools including DNA live-cell labeling technologies, RNA/ChIP-Seq analysis, and mass spectrometry analysis in appropriate infection models.