title: Time to seroconversion in HIV-exposed subjects carrying protective versus non protective KIR3DS1/L1 and HLA-B genotypes.
abstract: Natural killer (NK) cells play a role in the clearance of viral infections. Combinations of alleles at the polymorphic HLA-B locus and the NK cell surface killer immunoglobulin-like receptor locus KIR3DL1/S1 have been shown to influence time to AIDS in HIV-infected individuals and risk of seroconversion in HIV exposed seronegative (HESN) subjects. Here, we assessed time to seroconversion or duration of seronegative status in a group of 168 HIV exposed individuals, including 74 seroconverters and 94 HESN based on carriage or not of KIR3DL1/S1/HLA-B genotypes previously shown to be associated with protection from infection and/or slow time to AIDS. KIR3DL1/S1 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 to four-position resolution to resolve Bw4 and Bw6 alleles and the amino acid present at position 80. KIR3DL1/S1 heterozygotes became HIV infected significantly faster than KIR3DS1 homozygotes. Individuals who carried both KIR3DS1 and Bw4*80I did not remain HIV seronegative longer than those from a control group who were homozygous for HLA-Bw6 and carried no HLA-A locus Bw4 alleles Subjects who were *h/*y+B*57 showed a trend towards slower time to serconversion than those with other KIR3DL1 homozygous and KIR3DL1/S1 heterozygous genotypes. Thus, KIR3DS1 homozygosity is associated with protection from HIV infection while co-carriage of KIR3DS1 and Bw4*80I is not. The requirements for protection from HIV infection can differ from those that influence time to AIDS in HIV infected individuals.
authors.affiliation: Research Institute of the McGill University Health Centre (RI MUHC), Montréal, Québec, Canada; Division of Experimental Medicine, McGill University, Montréal, Québec, Canada.
authors.forename: Benjamin J M
authors.initials: BJ
authors.lastname: Tallon
authors.affiliation: Centre de recherche, Centre Hospitalier de l'Université de Montréal (CRCHUM), Montréal, Québec, Canada; Family Medicine Department, Université de Montréal, Montréal, Québec, Canada.
authors.forename: Julie
authors.initials: J
authors.lastname: Bruneau
authors.affiliation: Research Institute of the McGill University Health Centre (RI MUHC), Montréal, Québec, Canada; Division of Experimental Medicine, McGill University, Montréal, Québec, Canada; Division of Clinical Immunology and Allergy, McGill University Health Centre, Montréal, Québec, Canada.
authors.forename: Christos M
authors.initials: CM
authors.lastname: Tsoukas
authors.affiliation: Research Institute of the McGill University Health Centre (RI MUHC), Montréal, Québec, Canada; Immunodeficiency Service and Division of Hematology, Royal Victoria Hospital, McGill University Health Centre, Montréal, Québec, Canada.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Routy
authors.affiliation: Research Institute of the McGill University Health Centre (RI MUHC), Montréal, Québec, Canada; Division of Experimental Medicine, McGill University, Montréal, Québec, Canada.
authors.forename: Zahra
authors.initials: Z
authors.lastname: Kiani
authors.affiliation: Biostatistics Core Facility, Research Institute of the McGill University Health Centre, Montréal, Québec, Canada.
authors.forename: Xianming
authors.initials: X
authors.lastname: Tan
authors.affiliation: Research Institute of the McGill University Health Centre (RI MUHC), Montréal, Québec, Canada; Division of Experimental Medicine, McGill University, Montréal, Québec, Canada; Division of Clinical Immunology and Allergy, McGill University Health Centre, Montréal, Québec, Canada.
authors.forename: Nicole F
authors.initials: NF
authors.lastname: Bernard
mesh_terms: D000328:Adult; D000483:Alleles; D005260:Female; D056726:Genetic Association Studies; D005838:Genotype; D015658:HIV Infections / Q000235:genetics* / Q000276:immunology / Q000821:virology; D006679:HIV Seropositivity / Q000235:genetics* / Q000276:immunology; D015497:HIV-1 / Q000235:genetics / Q000276:immunology / Q000472:pathogenicity; D015234:HLA-A Antigens / Q000235:genetics* / Q000276:immunology; D015235:HLA-B Antigens / Q000235:genetics* / Q000276:immunology; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology; D008297:Male; D008875:Middle Aged; D054341:Receptors, KIR3DL1 / Q000235:genetics*
chemical_list: D015234:HLA-A Antigens; D015235:HLA-B Antigens; C038652:HLA-Bw6 antigen; C515083:KIR3DL1 protein, human; D054341:Receptors, KIR3DL1