Structural Insights into Reovirus σ1 Interactions with Two Neutralizing Antibodies

Area of Science:

• Structural biology
• Virology
• Immunology

Background:

• Reovirus attachment protein σ1 binds host cell receptors and is a target for neutralizing antibodies.
• Understanding antibody interactions with viral attachment proteins is crucial for developing antiviral strategies, especially for nonenveloped viruses.

Purpose of the Study:

• To structurally and functionally characterize two neutralizing antibodies targeting the reovirus σ1 attachment protein.
• To elucidate the mechanism of antibody-mediated reovirus neutralization and investigate conformational changes in σ1 during cell entry.

Main Methods:

• Crystal structure determination of antibody-σ1 complexes.
• Surface plasmon resonance and cell-binding assays to assess antibody binding and function.
• Hemagglutination inhibition assays to evaluate the effect of antibodies on glycan receptor engagement.

Main Results:

• Antibodies bind distinct epitopes on the σ1 head domain, sterically hindering junctional adhesion molecule-A (JAM-A) engagement.
• T1-specific antibody interferes with glycan binding in both virions and infectious subvirion particles (ISVPs).
• T3-specific antibody inhibits hemagglutination by virions but not ISVPs, suggesting conformational changes in σ1 during conversion.

Conclusions:

• Antibodies neutralize reovirus through steric hindrance of receptor binding sites.
• Structural rearrangement of the σ1 protein occurs during the transition from virion to ISVP.
• These findings provide insights into reovirus entry mechanisms and antibody-mediated neutralization.