Distinct cellular receptor interactions in poliovirus and rhinoviruses

Abstract

L.Xing and K.Tjarnlund contributed equally to this workReceptor binding to human poliovirus type 1 (PV1/M) and the major group of human rhinoviruses (HRV) was studied comparatively to uncover the evolution of receptor recognition in picornaviruses. Surface plasmon resonance showed receptor binding to PV1/M with faster association and dissociation rates than to HRV3 and HRV16, two serotypes that have similar binding kinetics. The faster rate for receptor association to PV1/M suggested a relatively more accessible binding site. Thermodynamics for receptor binding to the viruses and assays for receptor-mediated virus uncoating showed a more disruptive receptor interaction with PV1/M than with HRV3 or HRV16. Cryoelectron microscopy and image reconstruction of receptor-PV1/M complexes revealed receptor binding to the 'wall' of surface protrusions surrounding the 'canyon', a depressive surface in the capsid where the rhinovirus receptor binds. These data reveal more exposed receptor-binding sites in poliovirus than rhinoviruses, which are less protected from immune surveillance but more suited for receptor-mediated virus uncoating and entry at the cell surface.

Crystal structure of CD155 and electron microscopic studies of its complexes with polioviruses

“…S4). The footprint of CD155 onto the virus was well within the canyon, as had been observed (31)(32)(33)(34), and consisted of 3 roughly separate regions: in the ''north,'' ''southwest,'' and ''southeast'' of the canyon. Although the north and southwest regions are linked with each other in the base of the canyon, the southeastern region is separated by Ϸ10 Å (Fig.…”

“…Three earlier structural studies (31,32,34) had examined the interaction of PV with its receptor by using homology models in place of the actual PV receptor. Comparison of these homology models (31,32) with the structure of CD155 reported here gave rmsd between equivalent C␣ atoms in D1 of 3.6 and 3.1 Å, respectively, with the largest differences (up to 13.6 Å between C␣ atoms) being in the CCЈ, CЉD, DE, and FG loops.…”

“…The cryoEM studies (31)(32)(33)(34) of PVs complexed with their receptor CD155 were, at best, 16-Å resolution and were limited by the need to use homology models for CD155 that were based on Ig-like molecules that had Ͻ25% amino acid identity. The inaccuracy of the homology models would have influenced the determination of the contact residues in the virus-receptor interface.…”

The Structure of Echovirus Type 12 Bound to a Two-domain Fragment of Its Cellular Attachment Protein Decay-accelerating Factor (CD 55)

“…A radial depth-cue color scheme is used to indicate distance from the center of the virion (see the key). polioviruses and rhinoviruses, which have receptor affinities in the nanomolar range (49,50). The high quality of fit for the DAF 34 x-ray model in our reconstruction provides evidence of the relative rigidity of these two domains of the DAF molecule and contrasts strikingly with the flexibility observed in studies of a DAF 23 domain pair by NMR (33).…”

Distinct Kinetics for Binding of the CD46 and SLAM Receptors to Overlapping Sites in the Measles Virus Hemagglutinin Protein

“…Experiments were done at 10 and 20 l/min using Hepes buffer (pH 7.5) with 150 mM NaCl as running buffer. (15,20,25, and 30°) were determined from the kinetic rate constants as found in Table I. Averages for 3-4 experiments for each temperature are shown, with standard deviations in parentheses.…”