Killer-cell Immunoglobulin-like Receptor (KIR) gene profiles modify HIV disease course, not HIV acquisition in South African women

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Abstract

Background

Killer-cell Immunoglobulin-like Receptors(KIR) interact with Human Leukocyte Antigen(HLA) to modify natural killer- and T-cell function. KIR are implicated in HIV acquisition by small studies that have not been widely replicated. A role for KIR in HIV disease progression is more widely replicated and supported by functional studies.

Methods

To assess the role of KIR and KIR ligands in HIV acquisition and disease course, we studied at-risk women in South Africa between 2004–2010. Logistic regression was used for nested case–control analysis of 154 women who acquired vs. 155 who did not acquire HIV, despite high exposure. Linear mixed-effects models were used for cohort analysis of 139 women followed prospectively for a median of 54 months (IQR 31–69) until 2014.

Results

Neither KIR repertoires nor HLA alleles were associated with HIV acquisition. However, KIR haplotype BB was associated with lower viral loads (−0.44log10 copies/ml;SE = 0.18;p = 0.03) and higher CD4+ T-cell counts(+80 cells/μl;SE = 42;p = 0.04). This was largely explained by the protective effect of KIR2DL2/KIR2DS2 on the B haplotype and reciprocal detrimental effect of KIR2DL3 on the A haplotype.

Conclusions

Although neither KIR nor HLA appear to have a role in HIV acquisition, our data are consistent with involvement of KIR2DL2 in HIV control. Additional studies to replicate these findings are indicated.

Electronic supplementary material

The online version of this article (doi:10.1186/s12879-016-1361-1) contains supplementary material, which is available to authorized users.

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HIV-1 adaptation to NK cell mediated immune pressure

Galit Alter, David Heckerman, Arne Schneidewind … (2011)

Natural Killer (NK) cells play an important role in the control of viral infections, recognizing virally infected cells through a variety of activating and inhibitory receptors 1–3 . Epidemiological and functional studies have recently suggested that NK cells can also contribute to the control of HIV-1 infection through recognition of virally infected cells by both activating and inhibitory Killer Immunoglobulin-like receptors (KIRs) 4–7 . However, it remains unknown whether NK cells can directly mediate antiviral immune pressure in vivo in humans. Here we describe KIR-associated amino acid polymorphisms in the HIV-1 sequence of chronically infected individuals on a population level. We show that these KIR-associated HIV-1 sequence polymorphisms can enhance the binding of inhibitory KIRs to HIV-1-infected CD4+ T cells, leading to reduced antiviral activity of KIR+ NK cells. These data demonstrate that KIR+ NK cells can place immunological pressure on HIV-1, and that the virus can evade such NK cell mediated immune pressure by selecting for sequence polymorphisms, as previously described for virus-specific T cells and neutralizing antibodies 8 . NK cells might therefore play a previously underappreciated role in contributing to viral evolution.

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Author and article information

Contributors

V. Naranbhai:

ORCID: http://orcid.org/0000-0003-4281-8882

vivekn@well.ox.ac.uk

D. de Assis Rosa: debradeassisrosa@gmail.com

L. Werner: liesiew@gmail.com

R. Moodley: ramony111@gmail.com

H. Hong: heatherh@nicd.ac.za

A. Kharsany: KHARSANY@ukzn.ac.za

K. Mlisana: mlisanak@gmail.com

S. Sibeko: singeziwe@yahoo.com

N. Garrett: Nigel.Garrett@caprisa.org

D. Chopera: denis.chopera@gmail.com

W. H. Carr: wcarr@mec.cuny.edu

Q. Abdool Karim: Quarraisha.AbdoolKarim@caprisa.org

A. V. S. Hill: adrian.hill@ndm.ox.ac.uk

S. S. Abdool Karim: Salim.AbdoolKarim@caprisa.org

M. Altfeld: marcus.altfeld@hpi.uni-hamburg.de

C. M. Gray: clive.gray@uct.ac.za

T. Ndung’u: ndungu@ukzn.ac.za

Journal

Journal ID (nlm-ta): BMC Infect Dis

Journal ID (iso-abbrev): BMC Infect. Dis

Title: BMC Infectious Diseases

Publisher: BioMed Central (London )

ISSN (Electronic): 1471-2334

Publication date (Electronic): 25 January 2016

Publication date PMC-release: 25 January 2016

Publication date Collection: 2015

Volume: 16

Electronic Location Identifier: 27

Affiliations

[ ]Centre for the AIDS Programme of Research in South Africa (CAPRISA), University of KwaZulu-Natal, Durban, South Africa

[ ]Wellcome Trust Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK

[ ]HIV Pathogenesis Programme, University of KwaZulu-Natal, Durban, South Africa

[ ]National Institute of Communicable Diseases, Sandringham, South Africa

[ ]University of the Witwatersrand, Johannesburg, South Africa

[ ]University of Cape Town, Cape Town, South Africa

[ ]City University of New York - Medgar Evers College, New York, USA

[ ]Ragon Institute of MGH, MIT and Harvard University, Boston, USA

[ ]Mailman School of Public Health, Columbia University, New York, USA

[ ]Leibniz Institute for Experimental Virology, Heinrich Pette Institute, Hamburg, Germany

[ ]KwaZulu-Natal Research Institute for Tuberculosis and HIV, University of KwaZulu-Natal, Durban, South Africa

[ ]Max Planck Institute for Infection Biology, Chariteplatz, D-10117 Berlin, Germany

[ ]Division of Virology, School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa

Author information

V. Naranbhai http://orcid.org/0000-0003-4281-8882

Article

Publisher ID: 1361

DOI: 10.1186/s12879-016-1361-1

PMC ID: 4727384

PubMed ID: 26809736

SO-VID: d871f261-ca3e-48e0-9027-747a60d6e1a8

License:

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.