Table 1. Summary of the 22 potential CTL-escape mutations identified through statistical analysis.
Position States | Adjusted | Epitope Analysis | ||||||
HLA | Consensus | Polimorphism | HXB2 position | OR | p-value | p-value | Sequence | Known/predicted |
Correlations strongly supported as escape by phylogenetic correction | ||||||||
A03 | K | Q R | P028 | 21.0 | <10−7 | 0.0006 | RLRPGGKKK K | Known |
B57 | T | N | P242 | 54.7 | 0.0002 | 0.0013 | TSTLQEQIGWF | Known |
A11 | A | K M T V | P118 | 10.5 | 0.0018 | 0.0019 | KTQQAAADK | NetMHC |
A03 | E | D G | P055 | 4.8 | 0.0123 | 0.0139 | - | - |
Correlations moderately supported as escape by phylogenetic correction | ||||||||
B07 | G | S | P357 | 13.8 | 0.0050 | 0.0051 | GPGHKARVL | Known |
A24 | R | K | P030 | 0.21 | 0.0076 | 0.0070 | KYKLKHIVW | Known |
A11 | G | S | P357 | 13.2 | 0.0070 | 0.0063 | GVGGPGHKAR | Known |
A02 | Q | H | P065 | 4.8 | 0.0031 | 0.0025 | ILGQLQPSL | Epipred/NetMHC |
B40 | T | A | P081 | 5.8 | 0.0084 | 0.0076 | - | - |
A24 | V | L I | P046 | 3.4 | 0.0090 | 0.0082 | - | - |
Correlations inside known or predicted epitopes but not supported by phylogenetic correction | ||||||||
A02 | A | V | P083 | 0.13 | 0.0043 | 0.0038 | SLYNTVATL | Known |
A01 | GAP/N | S | P125 | NPC | 0.0105 | 0.0114 | NSSQVSQNY | Epipred/NetMHC |
Correlations neither inside known or predicted epitopes, nor supported as escape by phylogenetic correction (most likely false positives) | ||||||||
B49 | K | E Q A D | P012 | 0.00 | 0.0116 | 0.0127 | - | - |
B40 | Q | K R N | P090 | 0.00 | 0.0104 | 0.0102 | - | - |
A02 | A | P S T | P146 | 0.27 | 0.0099 | 0.0095 | - | - |
A01 | L | I V M | P215 | 0.00 | 0.0105 | 0.0108 | - | - |
A31 | T | S | P342 | 0.12 | 0.0063 | 0.0057 | - | - |
A31 | N | S T G | P372 | NPC | 0.0099 | 0.0089 | - | - |
B08 | T | V A | P303 | 4.0 | 0.0047 | 0.0044 | - | - |
B49 | E | D | P312 | 15.6 | 0.0119 | 0.0133 | - | - |
A01 | P | T S Q I | P339 | 4.9 | 0.0042 | 0.0032 | - | - |
A24 | T | S | P342 | 5.9 | 0.0110 | 0.0121 | - | - |
Detailed are the positions of the mutations in HXB2 Gag protein (http://www.hiv.lanl.gov/content/sequence/ LOCATE/locate.html, see Figure S1), the HLA allele associated, the most frequent aminoacidic residue found at each position (consensus) and the polymorphisms found in those positions. All of the associations shown in the table have a q-value lower than 0.2 (in our data set equivalent to an adjusted p-value lower than 0.0140). Mutations are classified accordingly to whether they were strongly, moderately or not supported by phylogenetic correction and to whether they were or not located within known or predicted epitopes. In black-cursive are highlighted positions where escape was identified and enlarged are anchor residues for binding with the HLA molecule. In column 9 is detailed whether the mutations was located within a known epitope (“Known”) according to Los Alamos Best-defined CTL/CD8+ Epitope Summary or predicted epitope according to the NetMHC 3.0 (“NetMHC”, CBS Prediction Server, Center for Biological Sequence Analysis, Technical University of Denmark) and/or Epipred softwares (“Epipred”, Microsoft Research). NPC: not possible to calculate.