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Updated: Jan 12, 2026

Isolation of Viral Replication Compartment-enriched Sub-nuclear Fractions from Adenovirus-infected Normal Human Cells
Published on: November 12, 2015
Adenovirus E1B-55K regulates p53-dependent and -independent gene expression during infection
Laura Seddar1, Konstantin von Stromberg1, Luca D Bertzbach1
1Leibniz Institute of Virology, Hamburg, Germany.
Abstract:
Human adenoviruses (HAdVs) are widespread pathogens with the capacity to manipulate host cellular pathways, including critical tumor suppressor networks. During oncogenic cell transformation, the adenoviral E1B-55K protein serves as a multifunctional viral regulator that, inter alia, modulates both p53-dependent and -independent pathways - though this function has been disputed in the context of viral infection. Here, we elucidate the dual role of E1B-55K in disrupting host defenses, focusing on its impact on p53 signaling and interferon-stimulated genes (ISGs) during infection. Using RNA-seq and follow-up experimental validation in A549 (p53 wildtype) and H1299 (p53-null) cells infected with wildtype HAdV-C5 or an E1B-55K-deficient mutant, we show that E1B-55K suppresses p53-mediated transcriptional responses. Concurrently, E1B-55K modulates ISG expression in a context-dependent manner. Our results reveal that E1B-55K leverages cellular context to optimize viral replication by targeting a host tumor suppressor and indicate interference with innate immune pathways. Our study thereby uncovers a previously underappreciated aspect of E1B-55K function during infection, offering insights into its repressive activity and solidifying its role as a multifunctional viral oncoprotein with broader implications for the HAdV replication cycle.
Insights
Human adenoviruses
Area of Science:
- Virology
- Molecular Biology
- Immunology
Background:
- Human adenoviruses (HAdVs) are common pathogens that can disrupt host cell functions.
- The viral protein E1B-55K is known to interact with tumor suppressor pathways, but its role during infection is debated.
- Understanding E1B-55K's function is crucial for comprehending HAdV pathogenesis.
Purpose of the Study:
- To investigate the role of the adenoviral E1B-55K protein in modulating host defenses during HAdV infection.
- To determine the impact of E1B-55K on p53 signaling and interferon-stimulated genes (ISGs).
Main Methods:
- RNA sequencing (RNA-seq) was performed on A549 (p53 wildtype) and H1299 (p53-null) cells infected with wildtype HAdV-C5 or an E1B-55K-deficient mutant.
- Experimental validation was conducted to confirm RNA-seq findings.
Main Results:
- E1B-55K was found to suppress p53-mediated transcriptional responses in infected cells.
- E1B-55K modulated the expression of interferon-stimulated genes (ISGs) in a context-dependent manner.
- These findings indicate E1B-55K targets host tumor suppressors and interferes with innate immunity.
Conclusions:
- E1B-55K plays a dual role in disrupting host defenses by targeting p53 and innate immune pathways.
- The cellular context influences E1B-55K's modulation of ISGs, optimizing viral replication.
- This study highlights a significant, previously underappreciated function of E1B-55K in HAdV infection and pathogenesis.
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