Using viral diversity to identify HIV-1 variants under HLA-dependent selection in a systematic viral genome-wide screen
Fig 2
Associations between HIV amino acid variants, HLA alleles, and average pairwise diversity interactions.
A) Shown are Gag242N:B*57:01 and 98 HLA/HIV-variant pairs with significant average pairwise diversity (APD)-HLA interactions (analysis Ιβ). Odds ratios (OR), sorted by effect size and HIV protein, are derived from Fisher’s exact tests, and colored by HLA genes (class Ι gray, class ΙΙ red). Pairs of interest are highlighted (bold label, triangle symbol). B) Multivariable logistic regressions of eight HLA/HIV-variant pairs of interest are shown. The effect of HLA allele, APD, and their interaction on the occurrence of the viral variant is presented as odds ratios with 95% confidence intervals (OR [CI]). Sample sizes are indicated (n). C) Distribution of the pairs Pol432R:A*03:01 (blue) and Rev57E:B*40:01 (red) within the study population and the likelihood of observing the variant in the presence (dark color) or absence (light color) of the HLA allele over APD is shown. Labels indicate the sample sizes for each group. Dashed lines represent the fitted values of linear regressions, while plain lines show data with standard error. D) Effect of APD on presence of viral variant (estimated OR from analysis Ιβ) in presence/absence of HLA allele. Coloration according to panel B. Positive interaction effects in yellow quadrant (= expected HLA escape mutation). *All estimates exceeding the third quartile+1.5 were adjusted to this threshold. Standardized APD used in panel B and D.