Viral surface geometry shapes influenza and coronavirus spike evolution through antibody pressure
Fig 1
Antibody targeting and mutability of the hemagglutinin protein for the seasonal flu.
(A-B) Coarse-grain model of the hemagglutinin trimer of A/New Caledonia/20/1999 (NC99) H1N1 influenza protein in its closed form (A). The virus model has 40 HA molecules at a spacing of 14.8 nm. [Measured spike spacing on influenza is 14 nm [78]] (B). For each immunogen geometry (trimer—A or full virus—B), a detailed atomistic structure of the immunogen is coarse-grained and presented in rainbow colors (panel i). Here every colored bead on the immunogen is a residue, representing a different HA epitope (228 different possible sites on trimeric HA). The antibody structure is presented as the Fc (blue bead), two arm (magenta beads) and antigen binding fragment (Fab) (yellow beads). Panels ii within A-B depict coarse-grained simulations for the on-rate of the Ab first arm binding (see Eq (S4)) to these residues [data from [24]]. The on-rates estimated from the simulation are superimposed on the HA structure. Top view (left), side view (right). The on-rate to cyan residues is high, intermediate to white residues, low for purple residues, and was the average of multiple simulations. (C) Panel i depicts the entropy (see Eq (1)) of HA epitopes computed for the seasonal flu (pre-pandemic influenza H1N1 (1918–1957 and 1977–2009) (sequences from [40]). Panel ii shows the entropy of the residues superimposed on HA structure, where highly mutable residues are in cyan, intermediate in white and conserved residues in purple.