The influence of HLA/HIV genetics on the occurrence of elite controllers and a need for therapeutics geotargeting view

Transcriptomic Signatures of Human Immunodeficiency Virus Post-Treatment Control

“…The proposed mechanisms of control exhibited by PTCs largely differ from those observed in HIV elite controllers. The model of elite control suggests provirus integration into transcriptionally silent regions of the host genome, which leads to a state of deep latency, as well as the killing of provirus-containing cells via host immune responses, such as CD8 1 T cell responses, that are associated with favorable HLA alleles (31,32). We propose that posttreatment control is not driven by preferential integration into noncoding host genomic regions, which should result in lower HIV transcription per provirus before ATI, but rather by cell intrinsic or extrinsic immune mechanisms after the expression of completed and spliced transcripts.…”

Mechanism of Viral Suppression among HIV Elite Controllers and Long-Term Nonprogressors in Nigeria and South Africa

“…The host genome feature that has been widely and most significantly reported as a correlate of the nonprogressive phenotype is the abundant representation of certain human leukocyte antigen (HLA) alleles, which are mostly found especially among ECs. The most correlating HLA alleles for elite control of HIV infection are HLA-B*57 and -B*27 [32,[43][44][45][46][47], although -B*58:01 has also been reported as a correlate of the nonprogressive phenotype in HIV infection as reported in two recent reviews [48,49]. The cytoplasmic domains of HLA-B alleles show higher resistance to Nef-enhanced immune disruption (on the antigen-presenting cells) compared to the HLA-A alleles; therefore, HLA-B alleles enhance better cytotoxic T-lymphocyte (CTL) recognition of HIV-infected cells, thereby enhancing optimum destruction of infected cells and eventually suppressing viral replication in HIV nonprogressors [29,46,49].…”

CD8+T-cell response to mutated HLA-B*35-restricted Gag HY9 and HA9 epitopes from HIV-1 variants from Medellin, Colombia

“…Among the HLA-I alleles, the HLA-B locus has the highest allelic diversity, which increases the repertoire of peptides that CD8 + T-cells can present [ 12 ]. In Colombia, the most frequent HLA-B allele is HLA-B*35 [ 13 ], an allele associated with rapid, but also with delayed progression of AIDS depending on the HLA-B*35 specific proteins and the circulating HIV-1 strains [ [14] , [15] , [16] , [17] , [18] ]. Interestingly, HLA-B*35 alleles are thought to display a greater diversity of self-peptides, leading to a lower probability of recognizing mutated viral epitopes compared to a CD8 + T-cell restricted by other HLA-I molecules [ 19 ].…”