HIV adaptation to HLA: Loss of Protection?
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HLA-B-restricted CD8+ T cell responses exert strong pressure on HIV replication and adaptation in HIV-infected individuals and are associated with delayed progression to AIDS. Development of escape mutations result in evasion of host immunity at the cost of viral fitness, causing both wild type and escape forms to be controlled by the host. Immune pressure is lost upon transmission to HLA-mismatched recipients, allowing for reversion. However, development of additional compensatory mutations restores viral fitness and eliminates the driving force behind reversion to wild type sequence, causing fixation of escape mutations in the HIV population. This thesis assesses the question what this will mean on the long term for HLA-B protectiveness in HIV infection throughout populations. In the literature study, I conclude that HLA-B alleles are likely to remain the most influential in controlling HIV vireamia in the future as these genes display the highest binding diversity of all HLA class I clades. Adaptation of HIV to current dominant protective CTL epitopes at one end of the epitope spectrum will cause formation of a new niche at the other end, allowing present subdominant protective immune responses to fit that niche and become more dominant in controlling HIV replication. The great binding promiscuity of HLA-B alleles when compared to other HLA clades will cause HIV to adapt more readily to these other clades. HLA-B’s binding diversity is therefore likely to ensure that these genes will remain the most influential in controlling HIV vireamia in the future. Obviously, the opposing forces driving escape mutations and sequence conservation will have a major influence on the direction that the adaptation of HIV will take on a population level, thereby influencing which current subdominant protective HLA-restricted immune responses will become dominant in the future.