Viral capsid structural assembly governs the reovirus binding interface to NgR1

Area of Science:

• Virology
• Structural Biology
• Neuroscience

Background:

• Viral entry mechanisms are critical for disease control.
• Nogo-receptor 1 (NgR1) mediates reovirus entry into the central nervous system.
• Understanding reovirus-NgR1 interactions is key to developing antiviral strategies.

Purpose of the Study:

• To investigate the molecular interactions between reovirus and Nogo-receptor 1 (NgR1).
• To explore how capsid architecture and receptor polymorphism affect virus binding.
• To elucidate the role of spatial configuration in the stability of the reovirus-NgR1 complex.

Main Methods:

• Employed single-molecule techniques to study virus-receptor interactions.
• Compared binding affinities of human and mouse NgR1 to reovirus μ1/σ3 proteins.
• Analyzed binding in isolated proteins, 2D capsid patches, and native 3D viral topology.

Main Results:

• Discovered a unique bivalent interaction between NgR1 and the reovirus capsid at heterohexamer interfaces.
• Demonstrated that the concave side of NgR1 is essential for binding.
• Confirmed that virus spatial organization and curvature critically influence reovirus-NgR1 complex stability.

Conclusions:

• The study provides novel insights into the structural basis of reovirus entry.
• Highlights the importance of studying molecular interactions in physiologically relevant spatial contexts.
• Opens new therapeutic avenues for controlling reovirus infections by targeting virus-host interactions.