We report the first atomic resolution structure of an animal virus, human rhinovirus 14. It is strikingly similar to known icosahedral plant RNA viruses. Four neutralizing immunogenic regions have been identified. These, and corresponding antigenic sequences of polio and foot-and-mouth disease viruses, reside on external protrusions. A large cleft on each icosahedral face is probably the host cell receptor binding site.

We conjecture that the binding of the receptor to HRV16 can occur only when the pocket is temporarily empty, when it is possible for the canyon floor to be deformed downwards into the pocket. We further propose that the role of the pocket factor is to stabilize virus in transit from one host cell to the next, and that binding of ICAM-1 traps the pocket in the empty state, destabilizing the virus as required for uncoating.

The observation of a partially occupied hydrophobic pocket in HRV16 forms a missing link between HRV14, which is always observed with no pocket factor in the native form, and rhinovirus 1A and other picornaviruses (e.g. poliovirus, coxsackievirus) which contain pocket factors. The pocket factor molecules probably regulate viral entry, uncoating and assembly. Picornavirus assembly is known to proceed via pentamers, therefore, the interaction of RNA with the conserved tryptophan residues across twofold axes between pentamers may play a role in picornavirus assembly. The positioning of a cation on the icosahedral fivefold axes and the structure of the N termini of VP4 and VP1 around these axes suggest a mechanism for the uncoating of rhinoviruses.

No abstract

A collection of 35 mouse monoclonal antibodies, raised against human rhinovirus 14 (HRV-14), was used to isolate 62 neutralization-resistant mutants. When cross-tested against the antibodies in a neutralization assay, the mutants fell into four antigenic groups, here called neutralization immunogens: NIm-IA,-IB,-II, and-III. Sequencing the mutant RNA in segments corresponding to serotype-variable regions revealed that the amino acid substitutions segregated into clusters, which correlated exactly with the immunogenic groups (NIm-IA mutants at VP1 amino acid residue 91 or 95; NIm-Il mutants at VP2 residue 158, 159, 161, or 162; NIm-Ill mutants at VP3 residue 72, 75, or 78; and NIm-IB mutants at two sites, either VP1 residue 83 or 85, or residue 138 or 139). Examination of the three-dimensional structure of the virus (M.