Genetic Variants in Nonclassical Major Histocompatibility Complex Class I Human Leukocyte Antigen (HLA)–E and HLA‐G Molecules Are Associated with Susceptibility to Heterosexual Acquisition of HIV‐1

Abstract

Human leukocyte antigen (HLA)-E and HLA-G molecules act as powerful modulators of the innate immune response. The present study shows that the HLA-E(G) genetic variant (the HLA-E*0103 allele) alone is significantly (P = .001) associated with a 4.0-fold decreased risk of human immunodeficiency virus 1 (HIV-1) infection in Zimbabwean women. Furthermore, women carrying the combination of the protective HLA-E(G) homozygote and HLA-G*0105N heterozygote genotypes had a 12.5-fold decreased risk of HIV-1 infection (P = .03), compared with women carrying neither genotype. These associations remained significant after adjustment was made for other significant sociodemographic risk factors for HIV prevalence in this population. In conclusion, HLA-E and HLA-G polymorphisms can independently and synergistically influence susceptibility to heterosexual acquisition of HIV-1.

Cutting Edge: Resistance to HIV-1 Infection among African Female Sex Workers Is Associated with Inhibitory KIR in the Absence of Their HLA Ligands

“…A recent study found genetic variants of HLA-E and HLA-G with a potentially lower affinity for their inhibitory NK cell receptors to be associated with a decreased risk of HIV transmission (26). These findings further support a role for NK cells in protection against virus transmission and suggest that parallel inhibitory NK receptor/HLA ligand mechanisms may be at play.…”

Evidence for the innate immune response as a correlate of protection in human immunodeficiency virus (HIV)-1 highly exposed seronegative subjects (HESN)

“…Additional evidence for the protective role of NK cells in resistance to HIV-1 stems from a genetic study linking variants in non-classical MHC class I HLA-E and HLA-G molecules with reduced susceptibility to heterosexual acquisition of HIV-1 [90]. Among the NK inhibitory receptors, the CD94/NKG2A receptor complex is unique in that it interacts specifically with the non-classical MHC protein, HLA-E, which presents leader peptides from the other classical MHC class I HLA-A, B, C molecules [83,84].…”

“…Among the NK inhibitory receptors, the CD94/NKG2A receptor complex is unique in that it interacts specifically with the non-classical MHC protein, HLA-E, which presents leader peptides from the other classical MHC class I HLA-A, B, C molecules [83,84]. Inheritance of the HLA-E*0103 genetic variant, which leads to increased surface expression of HLA-E proteins and heightened NK surveillance of virally infected cells that down-regulate MHC class 1 proteins, was associated with a decreased risk of human immunodeficiency virus 1 (HIV-1) infection in Zimbabwean women [90]. Similarly, women carrying the HLA-G*0105N genotype, resulting in a null HLA-G inhibitory protein that cannot inhibit NK cells, also have a significantly decreased risk of HIV-1 infection [90].…”

Association Between HLA‐E *0101 Homozygosity and Recurrent Miscarriage in Egyptian Women

“…The hypothesis of HLA-E allele homozygosity association with diseases was reported before in type 1 diabetes mellitus [23], nasopharyngeal carcinoma [24], HIV [25] and post-transplant complications [26,27]. Tamouza et al [26] was the first to report the association between HLA-E*0101 homozygosity and severe bacterial infections following HLA-matched unrelated donor hematopoietic stem cell transplantation and concluded that the presence of HLA-E*0101 allele could lead to inefficient presentation of bacterial peptides by the donor-derived antigen-presenting cells.…”

“…The selection of patients and control was carried out by systematic random sample. The mean age of the patients was 26.85 years (range [19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38], and the average number of RM was 4 (range 3-6). All women selected were not having any previous live births (primary miscarriage).…”