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Epstein-Barr virus encoded microRNAs target SUMO-regulated cellular functions

Simone Callegari1, Stefano Gastaldello, Omid R Faridani

  • 1Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden.

The FEBS Journal
|September 11, 2014
PubMed

Insights

Epstein-Barr virus microRNAs target the SUMOylation network, impacting cellular stress and immune responses. Viral miRNAs inhibit key pathways like TGF-beta, affecting viral replication and pathogenesis.

Area of Science:

  • Molecular Biology
  • Virology
  • Cellular Biology

Background:

  • Post-translational modification by SUMOylation regulates cellular stress responses and viral infections.
  • Epstein-Barr virus (EBV) encodes microRNAs (miRNAs) with poorly understood functions.
  • Understanding viral miRNA interactions with host cell machinery is crucial for pathogenesis research.

Purpose of the Study:

  • To investigate the interference of EBV-encoded miRNAs with the SUMOylation signaling network.
  • To identify host SUMO interactome members targeted by EBV miRNAs.
  • To elucidate the functional consequences of this interference on cellular processes and viral replication.

Main Methods:

  • Computational analysis of miRNA-mRNA target pairs to predict SUMO interactome members targeted by EBV miRNAs.
  • Functional network analysis of predicted target genes.
  • Experimental validation using lentiviral transduction and productive viral cycle induction.
  • Assessing the impact of BHRF1 miRNAs on TGF-beta signaling pathway components.

Main Results:

  • Identified 575 potential SUMO interactome targets of EBV miRNAs.
  • Predicted targets are enriched in functional networks controlling chromatin organization, stress, DNA damage, immune responses, apoptosis, and TGF-beta signaling.
  • Upregulation of BHRF1 miRNAs inhibited multiple components of the TGF-beta signaling pathway.

Conclusions:

  • EBV miRNAs can effectively interfere with SUMO-regulated cellular functions.
  • This interference impacts critical cellular processes involved in viral replication and pathogenesis.
  • Viral miRNAs represent a significant mechanism by which EBV manipulates host cell pathways.
Keywords:
EBVSUMOTGF-betamiRNAmiRNA tartget prediction

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