Common Genetic Variation and the Control of HIV-1 in Humans

Abstract

To extend the understanding of host genetic determinants of HIV-1 control, we performed a genome-wide association study in a cohort of 2,554 infected Caucasian subjects. The study was powered to detect common genetic variants explaining down to 1.3% of the variability in viral load at set point. We provide overwhelming confirmation of three associations previously reported in a genome-wide study and show further independent effects of both common and rare variants in the Major Histocompatibility Complex region (MHC). We also examined the polymorphisms reported in previous candidate gene studies and fail to support a role for any variant outside of the MHC or the chemokine receptor cluster on chromosome 3. In addition, we evaluated functional variants, copy-number polymorphisms, epistatic interactions, and biological pathways. This study thus represents a comprehensive assessment of common human genetic variation in HIV-1 control in Caucasians.

CD8 + T Cell Breadth and Ex Vivo Virus Inhibition Capacity Distinguish between Viremic Controllers with and without Protective HLA Class I Alleles

“…HLA class I typing was performed on genomic DNA samples extracted from blood at the time of enrollment as described previously (3). Of the 70 patients included in this study, 35 possessed protective HLA class I alleles (A*74:01, B*57, B*58:01, and B*81:01) (3,(13)(14)(15)(16)(17). These HLA alleles were selected as the principal protective alleles and are consistently the most protective that have been identified in the Durban study population (17,30,33).…”

“…HIV is able to evade immune responses by developing mutations that mediate escape from CTL recognition (6-12). In addition, the expression of certain HLA class I molecules by HIV-infected patients, such as HLA-B*27, HLA-B*57, HLA-B*58:01, HLA-B*81:01, and HLA-A*74: 01, is associated with better clinical disease outcomes in some population settings (3,(13)(14)(15)(16)(17)(18). HLA class I proteins present viral peptides on the surface of antigen-presenting cells to CTLs, and a major mechanism by which these protective alleles slow HIV disease progression is believed to be through CTL activity (18).…”

Major histocompatibility complex and its importance towards controlling infection

“…74 Furthermore, HLA-B*13:02 75,76 and B*58:01, 77-79 have also been described as favourable prognostic factors. The HLA-B*44 and HLA-B*57 have been described as favourable factors in both the acute and chronic phases of Sub Saharan Africans seroconverters regarding the association of HLA Class I alleles and protection against HIV infection.…”

Conventional Vaccine to Prevent AIDS A Paradigm or A Paradox? A SWOT Analysis

“…The HLA allele B*5701 has been reported as the host element in association with the endogenous retroviral element [77]. The impact of the ancestry of population with this allele has been investigated across populations from different parts of the world [78,79]. Systems biology in hands with a multidisciplinary approach has done a staticstical estimation for understanding the host-virus interaction.…”