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
Journal of Infectious Diseases
US Military HIV Research Program/Henry M Jackson Foundation, Walter Reed Army Institute of Research, 503 Robert Grant Avenue, Rm 2N27, Silver Spring, MD 20910, United States; Henry M Jackson Foundation, Rockville, MD, United States; Ragon Institute of Massachusetts General Hospital, Harvard University and Massachusetts Institute of Technology, Boston, MA, United States; Department of Infectious Diseases and Tropical Medicine, University of Munich, Munich, Germany; Division of Retrovirology, Walter Reed Army Institute of Research, Rockville, MD, United States; NIMR-Mbeya Medical Research Programme, Mbeya, Tanzania
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. © 2013 The Author 2013.
HLA A antigen; HLA antigen; HLA B antigen; killer cell immunoglobulin like receptor; Africa; article; cohort analysis; controlled study; disease predisposition; genetic polymorphism; human; human cell; Human immunodeficiency virus 1; innate immunity; natural killer cell; nonhuman; priority journal; prospective study; risk assessment; virus replication; virus strain; East Africa; HIV-1; HLA; innate immunity; KIR; sieve effect; subtypes; Genotype; HIV Infections; HIV Seroprevalence; HIV-1; HLA Antigens; Humans; Killer Cells, Natural; Odds Ratio; Polymorphism, Genetic; Prospective Studies; Receptors, KIR; Tanzania