Time to Seroconversion in HIV-Exposed Subjects Carrying Protective versus Non Protective KIR3DS1/L1 and HLA-B Genotypes

• Published in: PloS one Vol. 9; no. 10; p. e110480
• Main Authors: Tallon, Benjamin J. M., Bruneau, Julie, Tsoukas, Christos M., Routy, Jean-Pierre, Kiani, Zahra, Tan, Xianming, Bernard, Nicole F.
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 17.10.2014; Public Library of Science (PLoS)
• Subjects: Acquired immune deficiency syndrome; Adult; AIDS; AIDS (Disease); Alleles; Amino acids; Antigens; Biology and life sciences; Blood & organ donations; Cell surface; Exposure; Female; Genetic aspects; Genetic Association Studies; Genotype; Genotypes; Genotyping; Haplotypes; Health aspects; Health risks; Heterozygotes; Histocompatibility antigen HLA; HIV; HIV Infections - genetics; HIV Infections - immunology; HIV Infections - virology; HIV Seropositivity - genetics; HIV Seropositivity - immunology; HIV-1 - genetics; HIV-1 - immunology; HIV-1 - pathogenicity; HLA antigens; HLA-A Antigens - genetics; HLA-A Antigens - immunology; HLA-B Antigens - genetics; HLA-B Antigens - immunology; Homozygosity; Homozygotes; Human immunodeficiency virus; Humans; Immunoglobulins; Immunology; Infection; Infections; Killer Cells, Natural - immunology; Ligands; Loci; Major histocompatibility complex; Male; Medicine; Medicine and health sciences; Middle Aged; Natural killer cells; Physical Sciences; Polymerase chain reaction; Potassium channels (inwardly-rectifying); Primers; Receptors, KIR3DL1 - genetics; Seroconversion; Canada; Montreal Quebec Canada
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0110480

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.