Integrin α2β1 identified in cell models as ERAV receptor with dual glycan binding
Researchers established that equine rhinitis A virus enters cells via integrin α2β1, relying on specific protein and dual glycan interactions.
Researchers from Utrecht University, the University of Oxford, and The Pirbright Institute identified integrin α2β1 as the functional entry receptor for equine rhinitis A virus (ERAV) in cell culture models, according to a study published in Nature Communications doi.org
Nature Communicationsdoi.orgOpen source ↗. ERAV is a picornavirus related to the foot-and-mouth disease virus that causes respiratory infections in horses. The team used a CRISPR interference (CRISPRi) functional genomics screen in human HEK293T cells to isolate host factors required for infection, identifying the heterodimeric surface receptor α2β1.
Confirmation of the entry mechanism was obtained across multiple cell systems, including equine fibroblasts, through target knockout lines and receptor-blocking assays using antibodies and soluble receptors doi.org
Nature Communicationsdoi.orgOpen source ↗. When α2β1 integrin was blocked or depleted, viral entry was suppressed. Reconstitution experiments in receptor-depleted cells further verified that integrin α2β1 is directly required for mediating host cell infection.
Structural basis of receptor attachment
Cryo-electron microscopy and glycoproteomics revealed that ERAV attaches to the integrin while the complex is in its closed conformation doi.org
Nature Communicationsdoi.orgOpen source ↗. Viral binding occurs at the β-propeller domain of the α2 subunit and operates independently of divalent cations, unlike canonical integrin-ligand binding mechanisms.
Glycan dependencies in viral entry
High-resolution analysis showed that the interaction relies on direct contact with two separate host glycans: a high-mannose glycan linked to asparagine 112 (N112) of the α2 chain and a sialylated glycan at asparagine 269 (N269) of the β1 chain doi.org
Nature Communicationsdoi.orgOpen source ↗. The researchers tested glycan knockout and knock-in cellular models and reconstituted integrin-deficient cells with mutated receptor variants. These genetic modifications confirmed that both specific glycan linkages are essential for ERAV to infect host cells. The authors noted that this structural mechanism represents a previously unobserved combination of simultaneous protein and dual-glycan interactions facilitating viral host cell entry.
