Increased proportion of KIR3DS1 homozygotes in HIV-exposed uninfected individuals.
OBJECTIVE
Natural killer (NK) cell activity is increased in individuals who remain uninfected despite repeated exposures to HIV. Given that a combined major histocompatibility complex (MHC) class I and killer immunoglobulin-like receptor (KIR) KIR3D genotype has been linked to rate of HIV disease progression, we assessed whether these genotypes played a role in protection from infection.


METHODS
The study genotyped 80 HIV-exposed uninfected (EU) and 304 subjects in HIV primary infection (PI) at the MHC class IB and KIR3DS/L1 loci.


METHODS
KIR3D genotyping was performed by sequence-specific primer polymerase chain reaction using two pairs of specific primers for each locus. The MHC class IB locus was typed by sequence-specific oligonucleotide polymerase chain reaction and sequencing to resolve Bw4 and Bw6 alleles and the amino acid present at position 80.


RESULTS
Comparison of the genetic distribution of KIR3D, HLA Bw4 and HLA Bw4-I80 genotypes in EU versus PI subjects reveal an increased proportion of KIR3DS1 homozygotes in EU (11/80, 13.8%) compared to subjects in PI (16/304, 5.3%). Analyses of combined MHC class I and KIR3D expression show no differences between the two populations.


CONCLUSIONS
Homozygosity for the activating NK receptor KIR3DS1, may contribute to the more active NK cell function observed in EU and their relative resistance to HIV infection.
Boulet
Salix
S
Research Institute of the McGill University Health Centre, Montreal, Canada.
Sharafi
Saeid
S
Simic
Nancy
N
Bruneau
Julie
J
Routy
Jean-Pierre
JP
Tsoukas
Christos M
CM
Bernard
Nicole F
NF
D000328:Adult; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D018450:Disease Progression; D005260:Female; D005805:Genes, MHC Class I; D005838:Genotype; D015658:HIV Infections / Q000235:genetics / Q000276:immunology*; D018023:HIV Seronegativity / Q000235:genetics / Q000276:immunology*; D015235:HLA-B Antigens / Q000235:genetics; D006720:Homozygote; D006801:Humans; D007694:Killer Cells, Natural / Q000378:metabolism*; D008297:Male; D011446:Prospective Studies; D054349:Receptors, KIR3DS1 / Q000235:genetics*; D018401:Sample Size
D015235:HLA-B Antigens; C042388:HLA-Bw4 antigen; C038652:HLA-Bw6 antigen; D054349:Receptors, KIR3DS1