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

Rebecca N. Koehler; Galit Alter; Sodsai Tovanabutra; Elmar Saathoff; Miguel A. Arroyo; Anne M. Walsh; Eric E. Sanders-Buell; Leonard Maboko; Michael Hoelscher; Merlin L. Robb; Nelson L. Michael; Francine E. McCutchan; Jerome H. Kim; Gustavo H. Kijak

doi:10.1093/infdis/jit349

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

Rebecca N. Koehler, Galit Alter, Sodsai Tovanabutra, Elmar Saathoff, Miguel A. Arroyo, Anne M. Walsh, Eric E. Sanders-Buell, Leonard Maboko, Michael Hoelscher, Merlin L. Robb, Nelson L. Michael, Francine E. McCutchan, Jerome H. Kim, Gustavo H. Kijak^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

11 Scopus citations

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.

Original language	English
Pages (from-to)	1250-1254
Number of pages	5
Journal	Journal of Infectious Diseases
Volume	208
Issue number	8
DOIs	https://doi.org/10.1093/infdis/jit349
State	Published - 15 Oct 2013

Keywords

East Africa
HIV-1
HLA
KIR
innate immunity
sieve effect
subtypes

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10.1093/infdis/jit349

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Koehler, R. N., Alter, G., Tovanabutra, S., Saathoff, E., Arroyo, M. A., Walsh, A. M., Sanders-Buell, E. E., Maboko, L., Hoelscher, M., Robb, M. L., Michael, N. L., McCutchan, F. E., Kim, J. H., & Kijak, G. H. (2013). 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. Journal of Infectious Diseases, 208(8), 1250-1254. https://doi.org/10.1093/infdis/jit349

@article{809845090f074a49ba9a6db32833a0d6,

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",

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",

author = "Koehler, \{Rebecca N.\} and Galit Alter and Sodsai Tovanabutra and Elmar Saathoff and Arroyo, \{Miguel A.\} and Walsh, \{Anne M.\} and Sanders-Buell, \{Eric E.\} and Leonard Maboko and Michael Hoelscher and Robb, \{Merlin L.\} and Michael, \{Nelson L.\} and McCutchan, \{Francine E.\} and Kim, \{Jerome H.\} and Kijak, \{Gustavo H.\}",

note = "Funding Information: Financial support. This work was supported through a cooperative agreement between the Henry M. Jackson Foundation for the Advancement of Military Medicine and the US Department of Defense (DOD), by the National Institute for Allergy and Infectious Diseases (NIAID), and National Institutes of Health (NIH; grant Y01 AI2642-12). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The US Military HIV Research Program is jointly planned and funded by the DOD and NIAID/NIH by an interagency agreement. This manuscript was approved for publication by the Walter Reed Army Institute of Research. The views and opinions expressed herein are those of the authors and do not necessarily reflect those of the US Army or DOD or the NIH. Potential conflicts of interest. All authors: No reported conflicts.",

year = "2013",

month = oct,

day = "15",

doi = "10.1093/infdis/jit349",

language = "English",

volume = "208",

pages = "1250--1254",

journal = "Journal of Infectious Diseases",

issn = "0022-1899",

publisher = "Oxford University Press",

number = "8",

}

Koehler, RN, Alter, G, Tovanabutra, S, Saathoff, E, Arroyo, MA, Walsh, AM, Sanders-Buell, EE, Maboko, L, Hoelscher, M, Robb, ML , Michael, NL, McCutchan, FE, Kim, JH & Kijak, GH 2013, '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', Journal of Infectious Diseases, vol. 208, no. 8, pp. 1250-1254. https://doi.org/10.1093/infdis/jit349

TY - JOUR

T1 - Natural killer cell-mediated innate sieve effect on HIV-1

T2 - The impact of KIR/HLA polymorphism on HIV-1 subtype-specific acquisition in East Africa

AU - Koehler, Rebecca N.

AU - Alter, Galit

AU - Tovanabutra, Sodsai

AU - Saathoff, Elmar

AU - Arroyo, Miguel A.

AU - Walsh, Anne M.

AU - Sanders-Buell, Eric E.

AU - Maboko, Leonard

AU - Hoelscher, Michael

AU - Robb, Merlin L.

AU - Michael, Nelson L.

AU - McCutchan, Francine E.

AU - Kim, Jerome H.

AU - Kijak, Gustavo H.

N1 - Funding Information: Financial support. This work was supported through a cooperative agreement between the Henry M. Jackson Foundation for the Advancement of Military Medicine and the US Department of Defense (DOD), by the National Institute for Allergy and Infectious Diseases (NIAID), and National Institutes of Health (NIH; grant Y01 AI2642-12). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The US Military HIV Research Program is jointly planned and funded by the DOD and NIAID/NIH by an interagency agreement. This manuscript was approved for publication by the Walter Reed Army Institute of Research. The views and opinions expressed herein are those of the authors and do not necessarily reflect those of the US Army or DOD or the NIH. Potential conflicts of interest. All authors: No reported conflicts.

PY - 2013/10/15

Y1 - 2013/10/15

N2 - 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.

AB - 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.

KW - East Africa

KW - HIV-1

KW - HLA

KW - KIR

KW - innate immunity

KW - sieve effect

KW - subtypes

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U2 - 10.1093/infdis/jit349

DO - 10.1093/infdis/jit349

M3 - Article

C2 - 23922366

AN - SCOPUS:84885062929

SN - 0022-1899

VL - 208

SP - 1250

EP - 1254

JO - Journal of Infectious Diseases

JF - Journal of Infectious Diseases

IS - 8

ER -

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

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Keywords

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