Fig. 3.

Location and effect of independently associated amino acids. Three-dimensional structures of (A) HLA-B (PDB ID code 2bvp) and (B) HLA-A (PDB ID code 4hwz) proteins. Conditional analysis identified five independent amino acid positions [positions 97, 67, and 45 in HLA-B and positions 77 and 95 in HLA-A (orange residues)] that line the peptide-binding groove and explain the majority of the association signal in the MHC. (C) Effect on spVL (i.e., change in log₁₀ HIV-1 spVL per allele copy) of individual amino acid residues at each position. Results were calculated per allele using linear regression models, including allele dosage and principal components. Gray bars indicate the estimated change in spVL per amino acid allele at each position with standard error (whiskers). All identified positions accommodate >2 amino acid alleles, with allelic effects ranging from strongly protective (i.e., viral load decreasing) to deleterious (viral load increasing). Full association statistics and amino acid allele frequencies are listed in SI Appendix, Table S4.