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

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. © 2013 The Author 2013.