Integrin β1 Promotes Peripheral Entry by Rabies Virus

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.