Conservation of receptor contact residues amongst the arthritogenic alphaviruses. (a) The 48 residues on the E1/E2 Chikungunya virus (CHIKV) viral spike glycoproteins reported to make contact with the arthritogenic alphavirus receptor, MXRA8 [72] are aligned against the corresponding residues in o’nyong nyong virus (ONNV), Mayaro virus (MAYV) and RRV. Conservative and non-conservative substitutions are defined as described [86]. The complete sequence for ONNV IMTSSA 2004 was not available so residues E1 39-84 and E2 18-123 were derived from the closely related ONNV SG650 [62]; (b) The crystal structure of CHIKV E1/E2, with the receptor contact residues colored as in (a) for each of the indicated alphaviruses. Percentages indicate the percentage of identical contact residues relative to CHIKV; (c) Wild-type C57BL/6J mice were infected with CHIKV, ONNV MAYV or RRV. After 5 weeks, sera from each mouse was tested for its CHIKV neutralization titer. The neutralization titers were plotted against the % identity in E1/E2 receptor binding amino acids (left), the % identity in E1/E2 amino acids (middle) and % amino acid identity in the total genome (right). Statistics by Spearman’s correlations, p and rho indicated.