Identification of Site-Specific Adaptations Conferring Increased Neural Cell Tropism during Human Enterovirus 71 Infection
Figure 4
EV71 VP1 substitution locations relative to known receptors and capsid symmetry.
(A) EV71 VP1 model highlighting the BC loop (green) and positions of VP197R (red circle) and VP1167E (orange circle) relative to known receptors (gray). Eight known picornavirus VP1-receptor complexes (PDB codes along their sides) were structurally aligned to our model using the VP1 coordinates in each structure file. The distance (∼12 Å) between EV71 VP1 residue 97 and receptor surfaces is marked by vertical black dotted lines (distance between VP1 residue 97 and the 3dpr receptor, also ∼12 Å, is not marked). (B) Five EV71 VP197R model monomers arranged in capsid symmetry based on poliovirus capsid VP1 orientations (PDB 3epf). BC loops (green) and positions of residue 97 (red circles) and residue 167 (orange circles) are highlighted. (C) Side view of VP197R capsid assembly in B, rotated 80° on the plane of this page. The curvature and thickness of the capsid surface (based on PDB 3epf capsid assembly, VIPERdb) is represented as a light gray arc. (D) Sequence alignment of VP1 clinical isolates, EV71 substrain BrCr (Genbank U22521), and polivirus (PV1 (Genbank V01149), PV2 (M12197), PV3 (K01392)) surrounding EV71 VP197 and VP1167 substitutions. Index numbers refer to EV71 VP1 residue positions.