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Soluble receptor-resistant poliovirus mutants identify surface and internal capsid residues that control interaction
1Department of Microbiology, Columbia University College of Physicians & Surgeons, New York, NY 10032.
Abstract:
Poliovirus initiates infection by binding to its cell receptor and undergoing a receptor-mediated conformational alteration. To identify capsid residues that control these interactions, we have isolated and characterized poliovirus mutants that are resistant to neutralization by a soluble form of the poliovirus receptor. Twenty one soluble receptor-resistant (srr) mutants were identified which still use the poliovirus receptor to infect cells. All but one srr mutant contain a single amino acid change at one of 13 different positions, either on the surface or in the interior of the virion. The results of binding and alteration assays demonstrate that both surface and internal capsid residues regulate attachment to the receptor and conformational change of the virus. Mutations that reduce alteration also affect receptor binding, suggesting a common structural basis for early events in poliovirus infection.
Insights
Researchers identified poliovirus mutants resistant to receptor neutralization. These mutations, affecting surface and internal capsid residues, impact both virus attachment and conformational changes, revealing shared structural underpinnings for poliovirus infection entry.
Area of Science:
- Virology
- Structural Biology
- Molecular Biology
Background:
- Poliovirus infection begins with cell receptor binding and a conformational change.
- Understanding the capsid residues controlling these initial interactions is crucial for antiviral strategies.
Purpose of the Study:
- To identify specific poliovirus capsid residues involved in receptor binding and conformational alteration.
- To characterize mutants resistant to neutralization by soluble poliovirus receptor.
Main Methods:
- Isolation and characterization of poliovirus mutants resistant to soluble receptor neutralization.
- Analysis of single amino acid changes in identified mutants.
- Binding and conformational alteration assays to assess mutant function.
Main Results:
- Twenty-one soluble receptor-resistant (srr) mutants were identified, all utilizing the poliovirus receptor for infection.
- Nineteen mutants exhibited single amino acid substitutions at 13 distinct positions within the viral capsid.
- Both surface and internal capsid residues were found to regulate receptor attachment and conformational changes.
Conclusions:
- Capsid residues, both external and internal, play critical roles in poliovirus attachment and receptor-mediated conformational changes.
- A common structural basis likely underlies the regulation of these early poliovirus infection events.
- Identifying these residues provides insights into poliovirus entry mechanisms and potential therapeutic targets.