Increased proportion of KIR3DS1 homozygotes in HIV-exposed... : AIDS (original) (raw)

BASIC SCIENCE

Increased proportion of KIR3DS1 homozygotes in HIV-exposed uninfected individuals

Boulet, Salixa; Sharafi, Saeida; Simic, Nancya; Bruneau, Julieb; Routy, Jean-Pierrea; Tsoukas, Christos Ma; Bernard, Nicole Fa

From the aResearch Institute of the McGill University Health Centre, Montreal, Canada

bCentre de recherche du Centre Hospitalier de l'Université de Montréal, Montreal, Canada.

Received 6 June, 2007

Revised 20 October, 2007

Accepted 13 November, 2007

Correspondence to Dr Nicole F. Bernard, Research Institute of the McGill University Health Center, Montreal General Hospital, 1650 Cedar Ave. Rm C10-160, Montreal, Quebec, H3G 1A4, Canada. E-mail: [email protected]

Abstract

Objectives:

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.

Design:

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.