Nectin-like interactions between poliovirus and its receptor trigger conformational changes associated with cell...

Area of Science:

• Virology
• Structural Biology
• Biochemistry

Background:

• Poliovirus infection begins with attachment to the Pvr (CD155) receptor.
• Receptor binding at physiological temperatures causes irreversible virus expansion, exposing membrane-binding proteins.
• The mechanism by which receptor binding triggers this expansion remained unclear.

Purpose of the Study:

• To elucidate the structural mechanism of poliovirus expansion triggered by Pvr binding.
• To understand the role of the lipid ligand (pocket factor) in viral expansion.
• To propose hypotheses for capsid destabilization and RNA uncoating.

Main Methods:

• Cryo-electron microscopy at 4-Å resolution of poliovirus complexed with a modified Pvr ectodomain.
• Fitting of known atomic models of poliovirus and Pvr into experimental maps.
• Analysis of molecular interactions and structural rearrangements.

Main Results:

• A structure of poliovirus complexed with a partially deglycosylated Pvr ectodomain was determined.
• Poliovirus-Pvr interactions resemble nectin family interactions, involving burying of hydrophobic groups.
• Receptor binding displaces the lipid ligand, but this displacement alone does not cause irreversible expansion.

Conclusions:

• Receptor binding initiates structural changes in poliovirus, but additional rearrangements are needed for irreversible expansion.
• The findings provide a structural basis for understanding poliovirus entry.
• Analogies with nectin family binding suggest potential mechanisms for capsid destabilization and RNA release.