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Understanding Human-Virus Protein-Protein Interactions Using a Human Protein Complex-Based Analysis Framework.

Shiping Yang1, Chen Fu1, Xianyi Lian1

  • 1State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, China.

Msystems
|April 16, 2019
PubMed
Summary
This summary is machine-generated.

Viruses heavily target human protein complexes, with viral proteins often acting as scaffolds within these complexes. This study analyzes these virally targeted complexes (VTCs) to understand viral manipulation and discover new antiviral drug targets.

Keywords:
antiviral drug discoveryhuman-virus interactionnetworkprotein complexprotein-protein interaction

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Area of Science:

  • Computational biology and virology
  • Systems biology and network analysis
  • Molecular mechanisms of viral infection

Background:

  • Understanding viral infection requires analyzing host-virus interactions at a systems level.
  • Previous research focused on global protein-protein interaction (PPI) networks, neglecting local host network manipulations.
  • Viruses exploit host protein complexes, but computational analysis from this perspective is limited.

Purpose of the Study:

  • To computationally analyze human-virus protein-protein interactions (PPIs) within the context of human protein complexes.
  • To investigate virally targeted complexes (VTCs) for five common human viruses.
  • To identify patterns in VTCs, their functions, expression, and potential as antiviral drug targets.

Main Methods:

  • Integrated human-virus PPI data, human protein complex information, and gene expression profiles.
  • Performed large-scale analysis of VTCs for influenza A, HIV-1, Epstein-Barr virus, HPV, and HCV.
  • Characterized VTCs' properties, including subunit roles, essentiality, and expression patterns.

Main Results:

  • Viral targets are significantly enriched within human protein complexes.
  • Virally targeted proteins within complexes are often scaffolds and housekeeping proteins with high within-complex connectivity.
  • Essential complexes targeted by multiple viruses were identified, along with VTCs exhibiting periodic expression patterns potentially linked to cell cycle manipulation.

Conclusions:

  • Human protein complexes are crucial targets in viral infections, with viruses strategically manipulating them.
  • Analysis of VTCs provides insights into viral mechanisms and host cell cycle interference.
  • A VTC-based drug discovery strategy and the VTcomplex database offer valuable resources for antiviral research.