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. 2018 Sep 3;32(14):1927–1938. doi: 10.1097/QAD.0000000000001912

Fig. 2.

Human leukocyte antigen (HLA)-associated adaptations in HIV Pol, and their frequencies in Saskatchewan and CA/US.

Fig. 2

Panel a: The 70 HLA-associated adaptations in HIV subtype B Protease and the first 400 codons of RT, defined at q < 0.05 in an independent population-based study [38], that were investigated in the present analysis. Specific adaptations are shown in red, along with their restricting HLA, below the CA/US and Saskatchewan consensus Pol amino acid sequences. Nearby adaptations restricted by the same HLA allele are boxed together in yellow. For HLA-adapted variants that occur within an optimally-described HIV CTL epitope restricted by that allele [47], the published epitope sequence and HLA restriction are shown. In total, the 70 adaptations are restricted by 34 HLA class I alleles (6 HLA-A, 23 HLA-B and 5 HLA-C), occur at 52 Protease and RT codons, and include numerous experimentally verified immune escape mutations in optimally-described CTL epitopes (e.g., B∗51 : 01-RT- I135T that occurs at the C-terminus of the B∗51 : 01-restricted TI8 epitope and abrogates its ability to bind this allele [5,12,38]). The list includes HIV codons where the same adapted form is selected by distinct HLA alleles (e.g., both B∗07 : 02 and B∗07 : 05 select RT-S162C), codons where two or more adapted forms are described for the same allele at a given position (e.g., B∗51 : 01 normally selects RT-I135T but may also select I135 M) and codons where distinct alleles select opposing mutations (e.g., B∗51 : 01 selects I135T, while C∗12 : 03 induces pressure to maintain the global consensus I at this site). Panel b: Frequency comparison of HLA-associated adapted variants in HIV Protease in Saskatchewan versus CA/US, shown as linked pairs. Adapted variants with more than 10% higher frequency in Saskatchewan compared to CA/US are labeled in green; those with more than 10% lower frequency in Saskatchewan are labeled in black. Horizontal dotted line indicates the 5% frequency threshold used to define common HLA-adapted variants. Panels c, d: same as (b), for HLA-associated adapted variants in RT codons 1–250 and 251–400 respectively.