HIV-1 epitope repertoires and clinical data.

<p>Putative epitopes were identified <i>in silico</i> within full-length autologous HIV-1 proteomes and combined with previously described optimally defined CTL epitopes found in the LANL and IEDB databases. (A) and (B) respectively show the log viral loads and the CD4 counts plotted as a function of the number of predicted HIV-1 epitopes identified per proteome for the individuals with CD4 counts above 400 (n = 81). (C) Shows the number of predicted HIV-1 epitopes for individuals belonging to the highest (mean = 65) and lowest (mean = 76) viremia quartile. (D) Shows the average viral loads of individuals presenting a specific allele as a function of the average number of HIV-1 predicted epitopes for that allele (only alleles presented by at least 3 individuals in the South-African cohort were included).</p

Distribution of epitopes by HLA alleles and by protein.

<p>Distribution of epitopes among HIV-1 proteins for HLA alleles associated with lowest/highest viral loads. The ratio of predicted epitopes predicted for each protein corresponded to the number of epitope-fulfilling motifs identified in each protein over the total number of epitopes identified for the whole proteome. (A) Shows the distribution of epitopes for “good” alleles, i.e., those associated with the lowest viral loads in the cohort (lowest quartile: VL<125,437; mean = 65,384; median = 58,229). (B) Shows the epitope distribution for “bad” alleles, those associated with the highest viral loads in the cohort (highest quartile: VL>320,643; mean = 971,587; median = 531,208). For each allele belonging to a quartile, average values per allele were calculated based on the viral loads of HLA-matched individuals). (C) Illustrates the percentage of epitopes restricted by “good” and “bad” HLA alleles for each protein.</p

Relationship between CTL targeting and viremia.

<p>Protein-specific protective ratios were plotted as a function of the mean entropy of each HIV-1 protein. Protective ratios were calculated as the Log₁₀ of the viral load of all the individuals who did not mount a CTL response against a protein over the viral load of all the individuals who had one or more CTL response(s) directed against that protein.</p

Fitness competition assays between viruses mutated at residues in the sub-network associated with the HLA-B*81 epitope TPQDLNTML.

<p>The relative fitness of viruses presenting a mutation at site 177, 186 or at both sites is compared to that of the wt COT virus. Fitness competition assays were performed against a wt COT virus; the proportion of viral RNA from the mutant and wt viruses was measured at day zero, three and five (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0012463#s4" target="_blank">methods</a>).</p

Hubness across HIV-1 Subtype C Gag.

<p>The number of co-varying partners and the Shannon Entropy are represented for each site along the Gag protein. The blue (lower) part of the bars represent the number of AA-to-AA associations and the red (upper) part of the bars represent the number of HLA-to-AA associations at each site. The secondary axis refers to the Shannon Entropy at each site in Gag (continuous black line).</p

Amino Acid associations in HIV-1 subtype C Gag.

<p>Associations are depicted with a circular map: AA interactions among residues are represented with arcs, which are color-coded with a white to purple gradient – white corresponding to the strongest associations (i.e., lower q-values). HLA-restricted sites are identified by the HLA allele designations around the circle.</p

Relationship between viral loads and co-varying associations linking conserved sites.

<p>Shown are associations that involved an HLA-associated site (in bold) or at which a mutation had a significant impact on viral loads.</p>a<p>Number of individuals.</p>b<p>Consensus AA at both co-varying sites.</p>c<p>Rare residues at both co-varying sites.</p>d<p>Consensus AA at one site and a rare AA at the other co-varying site.</p