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.

Plos Pathogens
|November 3, 2025
PubMed

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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