Integrin αvβ1 Modulation Affects Subtype B Avian Metapneumovirus Fusion Protein-mediated Cell-Cell Fusion and Virus...

Area of Science:

• Virology
• Cell Biology
• Molecular Medicine

Background:

• Avian metapneumovirus (aMPV) fusion (F) protein mediates viral entry by fusing with host cell membranes.
• The specific host cell receptors for aMPV F protein remain unidentified.
• Subtype B aMPV (aMPV/B) F proteins possess a conserved Arg-Asp-Asp (RDD) motif.

Purpose of the Study:

• To identify the host cell receptor(s) for the aMPV/B F protein.
• To elucidate the role of the RDD motif in aMPV/B F protein-mediated membrane fusion and viral infection.

Main Methods:

• Integrin-specific peptide blocking assays.
• Antibody blocking and small interfering RNA (siRNA) knockdown of integrins αv and β1.
• Overexpression of integrin αv and β1 in non-permissive cells.
• Site-directed mutagenesis of the RDD motif to RAE (Arg-Ala-Glu).

Main Results:

• Integrin-specific peptides significantly reduced aMPV/B F protein fusogenicity and viral replication.
• Integrin αv and/or β1 were identified as mediators of aMPV/B F protein fusogenicity and viral replication.
• Overexpression of integrin αv and β1 in non-permissive cells enabled aMPV/B F protein binding and infection.
• Alteration of the RDD motif to RAE profoundly impaired aMPV/B F protein binding and fusogenic activity.

Conclusions:

• Integrin αvβ1 functions as a key receptor for aMPV/B F protein-mediated membrane fusion and viral infection.
• The RDD motif is critical for integrin binding and subsequent viral entry.
• These findings provide novel insights into the fusogenic mechanisms and pathogenesis of aMPV.