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Integrin β1 Promotes Peripheral Entry by Rabies Virus.

Lei Shuai1, Jinliang Wang1, Dandan Zhao1

  • 1State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, People's Republic of China.

Journal of Virology
|November 1, 2019
PubMed
Summary

Rabies virus uses integrin β1 (ITGB1) for cell entry, interacting with its glycoprotein. Targeting ITGB1 offers a potential therapy for rabies postexposure treatment.

Keywords:
fibronectinintegrin β1protein interactionrabies virusviral entry

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Area of Science:

  • Virology
  • Cell Biology
  • Immunology

Background:

  • Rabies virus (RABV) causes fatal zoonotic disease, but its cellular entry mechanisms remain incompletely understood.
  • Host factors are implicated in RABV invasion, yet specific cellular receptors and pathways are not fully elucidated.

Purpose of the Study:

  • To identify and characterize host factors involved in RABV cellular entry.
  • To investigate the role of integrin β1 (ITGB1) in RABV infection and its potential as a therapeutic target.

Main Methods:

  • Investigated RABV interaction with ITGB1 using knockdown and overexpression cell models.
  • Analyzed ITGB1 internalization and co-localization with RABV during infection.
  • Utilized ITGB1 ectodomain soluble protein, RGD peptide, and ITGB1-specific antibodies to neutralize RABV infection in vitro and in vivo.

Main Results:

  • Rabies virus utilizes integrin β1 (ITGB1) for cellular entry, demonstrated by reduced infection upon ITGB1 knockdown.
  • ITGB1 directly interacts with RABV glycoprotein and is internalized with the virus into late endosomes.
  • ITGB1-specific antibody and RGD peptide blocked RABV infection, particularly in peripheral tissues, highlighting ITGB1's role in RABV peripheral entry.

Conclusions:

  • Integrin β1 (ITGB1) is a critical host factor for rabies virus peripheral entry.
  • The interaction between ITGB1 and fibronectin is essential for RABV infection in peripheral tissues.
  • Targeting ITGB1 presents a promising therapeutic strategy for postexposure prophylaxis against rabies.