Natural Killer Cell-Mediated Innate Sieve Effect on HIV-1: The Impact of KIR/HLA Polymorphism on HIV-1 Subtype-Specific Acquisition in East Africa

Here we explore the association between killer cell immunoglobulin-like receptor (KIR)/HLA and human immunodeficiency virus type 1 (HIV-1) acquisition with different viral subtypes circulating in East Africa. In the prospective Cohort Development (CODE) cohort (Mbeya, Tanzania), carriers of KIR3DS1...

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Bibliographic Details
Published in:The Journal of infectious diseases 2013-10, Vol.208 (8), p.1250-1254
Main Authors: Koehler, Rebecca N., Alter, Galit, Tovanabutra, Sodsai, Saathoff, Elmar, Arroyo, Miguel A., Walsh, Anne M., Sanders-Buell, Eric E., Maboko, Leonard, Hoelscher, Michael, Robb, Merlin L., Michael, Nelson L., McCutchan, Francine E., Kim, Jerome H., Kijak, Gustavo H.
Format: Article
Language:English
Subjects:
Biological and medical sciences
Fundamental and applied biological sciences. Psychology
Genotype
HIV Infections - epidemiology
HIV Infections - genetics
HIV Infections - immunology
HIV Infections - virology
HIV Seroprevalence
HIV-1 - classification
HIV-1 - isolation & purification
HIV/AIDS
HLA Antigens - genetics
HLA Antigens - immunology
Human immunodeficiency virus 1
Humans
Infectious diseases
Killer Cells, Natural - chemistry
Killer Cells, Natural - immunology
Major and Brief Reports
Medical sciences
Microbiology
Miscellaneous
Odds Ratio
Polymorphism, Genetic
Prospective Studies
Receptors, KIR - genetics
Receptors, KIR - immunology
Tanzania - epidemiology
Virology
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Summary:Here we explore the association between killer cell immunoglobulin-like receptor (KIR)/HLA and human immunodeficiency virus type 1 (HIV-1) acquisition with different viral subtypes circulating in East Africa. In the prospective Cohort Development (CODE) cohort (Mbeya, Tanzania), carriers of KIR3DS1 and its putative ligand (HLA-A or HLA-B Bw4-80Ile alleles) showed increased HIV-1 acquisition risk (odds ratio [OR] = 3.46; 95% confidence interval [CI], 1.12-10.63; P = .04) and a trend for enrichment for subtype A and A-containing recombinants (78% vs 46%; OR = 4.05; 95% CI, .91-28.30; P = .09) at the expense of subtype C (11% vs 43%; OR = 0.17; 95% CI, .01-. 97; P = .08). In vitro, only natural killer cells from KIR3DS1(+)/HLA-Bw4-80Ile (+) healthy donors showed a 2-fold increased capacity to inhibit replication of subtype C vs subtype A viruses (P = .01). These findings suggest the presence of an innate sieve effect and may inform HIV-1 vaccine development.
ISSN:0022-1899
1537-6613
DOI:10.1093/infdis/jit349