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Early events in poliovirus infection: virus-receptor interactions
1Department of Microbiology, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA. racaniello@cuccfa.ccc.columbia.edu
Abstract:
The interaction of poliovirus with its cell receptor initiates conformational changes that lead to uncoating of the viral RNA. Three types of genetic analyses have been used to study the poliovirus-receptor interaction: (i) mutagenesis of the poliovirus receptor (PVR), (ii) selection of viral mutants resistant to neutralization with soluble PVR, and (iii) selection of viral variants adapted to use mutant PVRs. The results of these studies show that a small portion of the first immunoglobulin-like domain of PVR contacts viral residues within a deep depression on the surface of the capsid that encircles the fivefold axis of symmetry. Viral capsid residues that influence the interaction with PVR are also found in locations such as the capsid interior that cannot directly contact PVR. These mutations might influence the ability of the capsid to undergo receptor-mediated conformational transitions that are necessary for high-affinity interactions with PVR.
Insights
Poliovirus entry into cells involves receptor binding and RNA release. Genetic studies reveal specific viral and receptor interactions critical for this process, including indirect effects on capsid stability.
Area of Science:
- Virology
- Structural Biology
- Molecular Interactions
Background:
- Poliovirus binding to its cellular receptor (PVR) triggers essential conformational changes for viral RNA release.
- Understanding this interaction is key to developing antiviral strategies.
Purpose of the Study:
- To elucidate the specific molecular interactions between poliovirus and its receptor (PVR).
- To identify viral and PVR residues involved in the binding interface and their functional significance.
Main Methods:
- Genetic analyses including PVR mutagenesis.
- Selection of poliovirus mutants resistant to soluble PVR.
- Selection of viral variants adapted to mutant PVRs.
Main Results:
- A small region of the PVR's first immunoglobulin-like domain contacts poliovirus residues in a surface depression.
- Viral residues influencing PVR interaction are located both at the contact site and in the capsid interior.
- Interior mutations may affect receptor-mediated conformational changes crucial for high-affinity binding.
Conclusions:
- The poliovirus-PVR interaction interface is precisely defined, involving specific contact points.
- Indirect effects from non-contacting viral residues highlight the importance of capsid dynamics in receptor-mediated entry.
- This detailed understanding provides a basis for targeting viral entry mechanisms.