Influence of combinations of human major histocompatibility complex genes on the course of HIV–1 infection

Abstract

Major histocompatibility complex (MHC) genes (HLA in humans) regulate the immune response to foreign antigens. Molecular and serologic techniques were used to identify products of HLA class I, class II and transporter (TAP) genes (also part of the MHC) in homosexual seroconverters to human immunodeficiency virus type 1 (HIV-1). Comprehensive statistical analysis produced an HLA profile that predicted time from HIV-1 infection to the onset of AIDS. The profile was developed in a cohort of 139 men and evaluated in a second unrelated cohort of 102 men. In the evaluation cohort, the profile discriminated a sixfold difference between groups with the shortest and longest times to AIDS (P = 0.001). These findings support current theory about control of antigen processing by HLA genes and have implications for immunopathogenesis of HIV-1 and other infections.

MHC-I peptides get out of the groove and enable a novel mechanism of HIV-1 escape

“…The HLA-B*57:01 allele is associated with slower HIV-1 disease progression 15,16,17,18,19 and autoimmune reactions, including hypersensitivity, to the anti-viral drug abacavir 20,21,22 . In HIV-1-infected individuals, the expressed HLA-B*57:01 allomorph elicits robust CD8 + T-cell responses that are thought to control viremia.…”

Mhc class I haplotypes associated with survival time in simian immunodeficiency virus (SIV)-infected rhesus macaques

“…Several studies have shown (1) a temporal relationship between the decline of viral load and the emergence of CTL responses in both infected humans and infected monkeys, [3][4][5][6] (2) an increase of viral load after the appearance of CTL-escape HIV/SIV mutants during chronic and acute infection [7][8][9][10][11][12][13] and (3) a dramatic rise of viral load after CD8 þ T-cell depletion. [14][15][16] Additional indirect evidence for a CTL effect upon viral replication came from genetic association studies showing that Mhc class I alleles are strongly associated with survival time in HIV-infected humans [17][18][19][20] .…”

Distribution of TAP gene polymorphisms and extended MHC haplotypes in Mexican Mestizos and in Seri Indians from northwest Mexico

“…In fact, this has been shown for HIV infection. 22,23 The results on the contribution of these genes to the Table 1 Distribution of allele frequency of TAP1 and TAP2 genes in Seri Indians and in Mexican Mestizos †Previous equivalents, N = number of individuals; UD = undefined; AF = Allele frequency.…”