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- Title
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.
- Authors
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.
- 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.
- Subjects
EAST Africa; KILLER cells; HIV; CELL-mediated cytotoxicity; VACCINATION; IMMUNOCOMPETENT cells
- Publication
Journal of Infectious Diseases, 2013, Vol 208, Issue 8, p1250
- ISSN
0022-1899
- Publication type
Article
- DOI
10.1093/infdis/jit349