A combined genotype of KIR3DL1 high expressing alleles and HLA-B*57 is associated with a reduced risk of HIV infection.
OBJECTIVE
Coexpression of certain combinations of natural killer cell receptor KIR3DL1 and HLA-B alleles is associated with slower time to AIDS. The strongest protection in terms of disease outcome in KIR3DL1 homozygotes (3DL1 hmz) is coexpression of HLA-B*57 and a set of KIR3DL1 genotypes (3DL1*h/*y) lacking alleles expressed at low levels on natural killer cells. We questioned whether this allele combination could also influence resistance to infection.


METHODS
The genetic distribution of 3DL1*h/*y and HLA-B*57 was compared in 41 HIV-exposed uninfected and 186 recently HIV-infected 3DL1 hmz.


METHODS
KIR3DL1 subtyping was performed by sequencing the exons 3, 4, 5, 7-9. The major histocompatibility complex class IB locus was typed by sequence specific oligonucleotide PCR and sequencing to resolve Bw4 and Bw6 alleles and the amino acid present at position 80.


RESULTS
Percentage carriers of HLA-B*57 in HIV-exposed uninfected and individuals in a primary infection cohort was 12.2 and 4.3%, respectively (P = 0.0631), whereas that of 3DL1*h/*y was similar in both populations (P = 0.221). The 3DL1*h/*y-HLA-B*57 combined genotype was more frequent in exposed uninfected individuals (12.2%) than individuals in primary infection (2.7%) (P = 0.019; odds ratio, 5.03; 95% confidence intervals, 1.38-18.3).


CONCLUSIONS
Coexpression of 3DL1*h/*y and B*57, which has been associated with a reduced risk of progressing to AIDS in HIV-infected individuals also lowers the risk of HIV infection in exposed uninfected individuals.
Boulet
Salix
S
Research Institute of the McGill University Health Centre, Canada.
Kleyman
Marianna
M
Kim
Jenice Yj
JY
Kamya
Philomena
P
Sharafi
Saeid
S
Simic
Nancy
N
Bruneau
Julie
J
Routy
Jean-Pierre
JP
Tsoukas
Christos M
CM
Bernard
Nicole F
NF
D000483:Alleles; D002478:Cells, Cultured; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D015658:HIV Infections / Q000235:genetics* / Q000276:immunology; D015497:HIV-1; D015235:HLA-B Antigens / Q000235:genetics*; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics; D054341:Receptors, KIR3DL1 / Q000235:genetics*
D015235:HLA-B Antigens; C103707:HLA-B57 antigen; C515083:KIR3DL1 protein, human; D054341:Receptors, KIR3DL1