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the viral RNA. Contact between the virus and receptor occurs through capsid residues in the canyon and the C′-C″ ridge on domain 1 of PVR. High-affinity binding is probably dependent on the nature of the contact residues in the virus and the receptor and on capsid residues at the protomer interface and in the interior that allow the capsid to conform to the receptor. Because the contact points in the canyon are located at the protomer interface, above the hydrocarbon-binding pocket, the interaction with PVR may destabilize the interface and weaken the affinity of sphingosine for the pocket. As additional PVR molecules bind to the capsid, sphingosine may be released, leading to complete destabilization of the capsid. The RNA might then emerge from a portal at the protomer interface. Crystallographic resolution of the virus-receptor complex will be required to demonstrate precisely how the virus and receptor interact. Whether or not PVR, either in soluble form or associated with membranes, is sufficient to drive RNA uncoating can also be determined experimentally. Finally, the location in the cell at which the uncoating event occurs must be identified. These experiments will provide clues about how cell receptors participate in the uncoating of an icosahedral virus.

Work cited from my laboratory has been supported by the National Institutes of Health and the American Cancer Society.

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