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

J Infect Dis. 2013 Oct 15;208(8):1250-4. doi: 10.1093/infdis/jit349. Epub 2013 Aug 6.

Abstract

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.

Keywords: East Africa; HIV-1; HLA; KIR; innate immunity; sieve effect; subtypes.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Genotype
  • HIV Infections / epidemiology
  • HIV Infections / genetics
  • HIV Infections / immunology*
  • HIV Infections / virology*
  • HIV Seroprevalence
  • HIV-1 / classification*
  • HIV-1 / isolation & purification
  • HLA Antigens / genetics*
  • HLA Antigens / immunology
  • Humans
  • Killer Cells, Natural / chemistry
  • Killer Cells, Natural / immunology*
  • Odds Ratio
  • Polymorphism, Genetic
  • Prospective Studies
  • Receptors, KIR / genetics*
  • Receptors, KIR / immunology
  • Tanzania / epidemiology

Substances

  • HLA Antigens
  • Receptors, KIR