Project Details
Projekt
Understanding the type-specific role of novel virus-SUMO interplay during AdV infection to orchestrate immunoproteasomes and IFN response
Applicant
Professorin Dr. Sabrina Schreiner
Subject Area
Virology
Biochemistry
Cell Biology
Biochemistry
Cell Biology
Term
since 2026
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 548065690
Human adenoviruses (HAdVs) are non-enveloped DNA viruses causing diseases from mild infections to severe, often fatal outcomes in immunocompromised hosts. Despite their relevance and use as gene and vaccine vectors, key mechanisms of HAdV-host interaction remain unclear. Current knowledge focuses on HAdV-C5, overlooking significant interspecies differences in genome structure, replication, and immune modulation crucial for safe and effective vector design. During productive infection, HAdVs express early viral genes that colocalize with nuclear promyelocytic leukemia protein nuclear bodies (PML-NBs) to degrade or displace key host regulators frequently linked to SUMO posttranslational modification (PTM). PML-NBs can either inhibit or promote viral gene expression, depending on the context. Their integrity is disrupted during HAdV-C5 infection, leading to the formation of PML tracks within the host nucleus, which in turn support viral gene expression, replication, and progeny production. However, the type-specific mechanisms by which HAdVs modulate PML-NBs and how these alterations affect immunoproteasome (iP) biogenesis and interferon (IFN) responses through changes in SUMOylation remain largely unexplored. This project aims to address these critical knowledge gaps for the often-neglected non-C5 HAdV types relevant for both infection and vector applications. Specifically, we will (i) systematically investigate the fate of PML-NBs and SUMO conjugation during infection and their role in immune recognition and response, (ii) elucidate the consequences of these interactions for iP biogenesis and core components (LMP3/7, MECL1, PA28γ), and (iii) determine how the transcription factor PU.1 - essential for iP regulation - is targeted and functionally suppressed via the viral E1A-p300-PML axis. By defining the type-specific interplay between viral proteins, SUMO modification, and host immune regulation, this research will provide new insights into the molecular strategies by which HAdVs manipulate cellular defense systems. The results will not only advance fundamental understanding of adenoviral pathogenesis but also inform the rational design of safer and more effective adenoviral vectors for therapeutic applications. Ultimately, this work will open new avenues for antiviral intervention and immunomodulatory strategies that bridge the gap between basic virology and translational medicine.
DFG Programme
Research Units
