HIV Nef polymorphisms overrepresented in subjects with HIV-associated PAH. Individual variations (using one-letter amino acid codes, numbered, colored, and indicated by arrows) are indicated in cartoons of Nef crystal structures. The Nef structure data are available as separate models.15 We used the models of (A) myristoylated Nef anchor domain, which includes Nef amino acids 2–57, and (B) Nef core to the C-terminus (amino acids 56–206). Alpha-helixes are colored in pink, beta-sheets are in orange. The N- and C-termini are indicated in each model. Nonconservative polymorphisms are indicated in yellow. Of the 10 polymorphisms identified in European subjects with HIV-associated PAH, seven were also found in the cohort from San Francisco (underlined). Refer to Supplementary Table S1 for frequency data. Symbol: ▾ indicates hydrophilic amino acid.