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Authors
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M.A.Oliveira,
R.Zhao,
W.M.Lee,
M.J.Kremer,
I.Minor,
R.R.Rueckert,
G.D.Diana,
D.C.Pevear,
F.J.Dutko,
M.A.McKinlay.
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BACKGROUND: Rhinoviruses and the homologous polioviruses have hydrophobic
pockets below their receptor-binding sites, which often contain unidentified
electron density ('pocket factors'). Certain antiviral compounds also bind in
the pocket, displacing the pocket factor and inhibiting uncoating. However,
human rhinovirus (HRV)14, which belongs to the major group of rhinoviruses that
use intercellular adhesion molecule-1 (ICAM-1) as a receptor, has an empty
pocket. When antiviral compounds bind into the empty pocket of HRV14, the roof
of the pocket, which is also the floor of the receptor binding site (the
canyon), is deformed, preventing receptor attachment. The role of the pocket in
viral infectivity is not known. RESULTS: We have determined the structure of
HRV16, another major receptor group rhinovirus serotype, to atomic resolution.
Unlike HRV14, the pockets contain electron density resembling a fatty acid,
eight or more carbon atoms long. Binding of the antiviral compound WIN 56291
does not cause deformation of the pocket, although it does prevent receptor
attachment. CONCLUSIONS: 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.
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