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

作者：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^*

来源：Journal of Infectious Diseases, 2013, 208(8): 1250-1254.

DOI：10.1093/infdis/jit349

• HIV-1
• innate immunity
• KIR
• HLA
• sieve effect
• subtypes
• 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 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.

• 出版日期2013-10-15