A Whole-Genome Association Study of Major Determinants for Host Control of HIV-1

Abstract

Understanding why some people establish and maintain effective control of HIV-1 and others do not is a priority in the effort to develop new treatments for HIV/AIDS. Using a whole-genome association strategy, we identified polymorphisms that explain nearly 15% of the variation among individuals in viral load during the asymptomatic set-point period of infection. One of these is found within an endogenous retroviral element and is associated with major histocompatibility allele human leukocyte antigen (HLA)-B*5701, whereas a second is located near the HLA-C gene. An additional analysis of the time to HIV disease progression implicated two genes, one of which encodes an RNA polymerase I subunit. These findings emphasize the importance of studying human genetic variation as a guide to combating infectious agents.

Skewing of the NK Cell Repertoire by MHC Class I via Quantitatively Controlled Enrichment and Contraction of Specific Ly49 Subsets

“…Functional education of human NK cells by HLA class I is well established (13,15,(39)(40)(41)(42), and a quantitative influence of HLA on NK cell responsiveness may explain, for example, how a single nucleotide polymorphism associated with a higher HLA-C expression levels is beneficial in acute HIV infection (43,44). The role of HLA class I molecules on the human NK cell repertoire is less clear, but is implied from studies showing that specific compound genotypes of KIR and HLA may provide protection or susceptibility to infections, cancers, and successful pregnancy (45).…”

Admixture as the basis for genetic mapping

“…mouse, Arabidopsis, human), association mapping has become feasible at the scale of the entire genome, with a high likelihood of markers in linkage disequilibrium with genes underlying traits of interest (e.g. [14,81,82]). Consequently, both approaches now can involve mapping across the genome.…”

HIV/AIDS: 30 Years of progress and future challenges

“…Particular HLA genotypes (e.g. HLA-B57, B27, and B51) are repeatedly linked with long-term survival and slow HIV disease progression [56,85]. These findings suggest that the recognition of some epitopes within the HIV proteome allows for improved control of virus replication.…”