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Poliovirus variants selected on mutant receptor-expressing cells identify capsid residues that expand receptor
1Department of Microbiology, Columbia University College of Physicians & Surgeons, New York, New York 10032, USA.
Abstract:
Mutations in the predicted C'-C"-D edge of the first immunoglobulin-like domain of the poliovirus receptor were previously shown to eliminate poliovirus binding. To identify capsid residues that expand receptor recognition, 16 poliovirus suppressor mutants were selected that replicate in three different mutant receptor-expressing cell lines as well as in cells expressing the wild-type receptor. Sequence analysis of the mutant viruses revealed three capsid residues that enable poliovirus to utilize defective receptors. Two residues are in regions of the capsid that are known to regulate receptor binding and receptor-mediated conformational transitions. A third residue is located in a highly exposed loop on the virion surface that controls poliovirus host range in mice by influencing receptor recognition. One of the suppressor mutations enables the primate-restricted P1/Mahoney strain to paralyze mice by enabling the virus to recognize a receptor in the mouse central nervous system. Capsid mutations that suppress receptor defects may exert their effect at the binding site or may improve receptor binding by regulating structural transitions of the capsid.
Insights
Researchers identified three poliovirus capsid mutations that allow the virus to bind to defective receptors. One mutation enables a primate-specific strain to infect mice by recognizing mouse receptors.
Area of Science:
- Virology
- Molecular Biology
- Structural Biology
Background:
- Poliovirus binding relies on specific interactions with its receptor.
- Mutations in the poliovirus receptor's immunoglobulin-like domain disrupt virus binding.
- Understanding poliovirus-receptor interactions is key to viral pathogenesis and control.
Purpose of the Study:
- To identify poliovirus capsid residues that enable recognition of defective receptors.
- To investigate how capsid mutations can overcome receptor-binding deficiencies.
- To explore mechanisms of poliovirus host range expansion.
Main Methods:
- Selection of poliovirus suppressor mutants replicating on mutant receptor cell lines.
- Sequence analysis of identified poliovirus mutants.
- Characterization of capsid residue function in receptor recognition and host adaptation.
Main Results:
- Identified three critical poliovirus capsid residues that restore binding to defective receptors.
- Two residues are located in known receptor-binding and conformational transition regions.
- A third residue, in an exposed surface loop, influences host range by affecting receptor recognition.
- One mutation allows a primate-adapted strain to infect and paralyze mice by utilizing mouse receptors.
Conclusions:
- Poliovirus capsid mutations can restore function by interacting with altered receptor sites.
- Suppression of receptor defects can occur through direct binding site modification or allosteric regulation of capsid structure.
- These findings provide insights into viral adaptation and the evolution of host tropism.