Intrinsic Disorder in the Host Proteins Entrapped in Rabies Virus Particles

Hafiza Nimra Ashraf1, Vladimir N Uversky1,2

  • 1Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA.

Viruses
|June 27, 2024
PubMed

Insights

Rabies virus (RABV) entraps disordered host proteins crucial for its pathogenicity and immune evasion. Targeting these intrinsically disordered proteins (IDPs) offers potential therapeutic strategies against rabies.

Area of Science:

  • Virology
  • Proteomics
  • Structural Biology

Background:

  • Rabies virus (RABV) infection poses a significant global health threat.
  • Understanding virus-host interactions is key to developing effective antiviral strategies.

Purpose of the Study:

  • To investigate the role of host proteins entrapped within purified RABV particles.
  • To analyze the intrinsic disorder of these host proteins and their potential contribution to rabies pathogenesis.

Main Methods:

  • Proteomics analysis of purified RABV.
  • Bioinformatic analysis using tools like FuzDrop, D2P2, UniProt, RIDAO, STRING, AlphaFold, and ELM.
  • Focus on five highly disordered mouse proteins: Neuromodulin, Chmp4b, DnaJB6, Vps37B, and Wasl.

Main Results:

  • 47 host proteins were identified within RABV particles, with 11 exhibiting high intrinsic disorder.
  • Detailed analysis of five specific disordered proteins revealed their potential roles in viral pathogenicity.
  • Suggested involvement in immune evasion and antiviral drug resistance.

Conclusions:

  • Intrinsically disordered proteins (IDPs) play a critical role in RABV pathogenesis.
  • Disordered host-virus interactions represent a potential therapeutic target for rabies treatment.

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