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 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.
US Military HIV Research Program.
Rebecca N
RN
Koehler
Galit
G
Alter
Sodsai
S
Tovanabutra
Elmar
E
Saathoff
Miguel A
MA
Arroyo
Anne M
AM
Walsh
Eric E
EE
Sanders-Buell
Leonard
L
Maboko
Michael
M
Hoelscher
Merlin L
ML
Robb
Nelson L
NL
Michael
Francine E
FE
McCutchan
Jerome H
JH
Kim
Gustavo H
GH
Kijak
D005838:Genotype; D015658:HIV Infections / Q000453:epidemiology / Q000235:genetics / Q000276:immunology* / Q000821:virology*; D015528:HIV Seroprevalence; D015497:HIV-1 / Q000145:classification* / Q000302:isolation & purification; D006680:HLA Antigens / Q000235:genetics* / Q000276:immunology; D006801:Humans; D007694:Killer Cells, Natural / Q000737:chemistry / Q000276:immunology*; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D054340:Receptors, KIR / Q000235:genetics* / Q000276:immunology; D013636:Tanzania / Q000453:epidemiology
D006680:HLA Antigens; D054340:Receptors, KIR
East Africa; HIV-1; HLA; KIR; innate immunity; sieve effect; subtypes