Bashirova, AA and Martin-Gayo, E and Jones, DC and Qi, Y and Apps, R and Gao, X and Burke, PS and Taylor, CJ and Rogich, J and Wolinsky, S and Bream, JH and Duggal, P and Hussain, S and Martinson, J and Weintrob, A and Kirk, GD and Fellay, J and Buchbinder, SP and Goedert, JJ and Deeks, SG and Pereyra, F and Trowsdale, J and Lichterfeld, M and Telenti, A and Walker, BD and Allen, RL and Carrington, M and Yu, XG
(2014)
LILRB2 Interaction with HLA Class I Correlates with Control of HIV-1 Infection.
PLoS Genetics, 10 (3).
ISSN 1553-7390
Abstract
Natural progression of HIV-1 infection depends on genetic variation in the human major histocompatibility complex (MHC) class I locus, and the CD8+ T cell response is thought to be a primary mechanism of this effect. However, polymorphism within the MHC may also alter innate immune activity against human immunodeficiency virus type 1 (HIV-1) by changing interactions of human leukocyte antigen (HLA) class I molecules with leukocyte immunoglobulin-like receptors (LILR), a group of immunoregulatory receptors mainly expressed on myelomonocytic cells including dendritic cells (DCs). We used previously characterized HLA allotype-specific binding capacities of LILRB1 and LILRB2 as well as data from a large cohort of HIV-1-infected individuals (N = 5126) to test whether LILR-HLA class I interactions influence viral load in HIV-1 infection. Our analyses in persons of European descent, the largest ethnic group examined, show that the effect of HLA-B alleles on HIV-1 control correlates with the binding strength between corresponding HLA-B allotypes and LILRB2 (p = 10-2). Moreover, overall binding strength of LILRB2 to classical HLA class I allotypes, defined by the HLA-A/B/C genotypes in each patient, positively associates with viral replication in the absence of therapy in patients of both European (p = 10-11-10-9) and African (p = 10-5-10-3) descent. This effect appears to be driven by variations in LILRB2 binding affinities to HLA-B and is independent of individual class I allelic effects that are not related to the LILRB2 function. Correspondingly, in vitro experiments suggest that strong LILRB2-HLA binding negatively affects antigen-presenting properties of DCs. Thus, we propose an impact of LILRB2 on HIV-1 disease outcomes through altered regulation of DCs by LILRB2-HLA engagement.
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Item Type: |
Article
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Status: |
Published |
Creators/Authors: |
Creators | Email | Pitt Username | ORCID |
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Bashirova, AA | | | | Martin-Gayo, E | | | | Jones, DC | | | | Qi, Y | | | | Apps, R | | | | Gao, X | | | | Burke, PS | | | | Taylor, CJ | | | | Rogich, J | | | | Wolinsky, S | | | | Bream, JH | | | | Duggal, P | | | | Hussain, S | | | | Martinson, J | jmartins@pitt.edu | JMARTINS | | Weintrob, A | | | | Kirk, GD | | | | Fellay, J | | | | Buchbinder, SP | | | | Goedert, JJ | | | | Deeks, SG | | | | Pereyra, F | | | | Trowsdale, J | | | | Lichterfeld, M | | | | Telenti, A | | | | Walker, BD | | | | Allen, RL | | | | Carrington, M | | | | Yu, XG | | | |
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Contributors: |
Contribution | Contributors Name | Email | Pitt Username | ORCID |
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Editor | Barsh, Gregory S. | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED |
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Date: |
1 January 2014 |
Date Type: |
Publication |
Journal or Publication Title: |
PLoS Genetics |
Volume: |
10 |
Number: |
3 |
DOI or Unique Handle: |
10.1371/journal.pgen.1004196 |
Schools and Programs: |
School of Public Health > Infectious Diseases and Microbiology |
Refereed: |
Yes |
ISSN: |
1553-7390 |
Date Deposited: |
01 Jul 2014 16:13 |
Last Modified: |
22 Jun 2021 13:56 |
URI: |
http://d-scholarship.pitt.edu/id/eprint/22120 |
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