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Enrichment of HLA types and single-nucleotide polymorphism associated with non-progression in a strictly defined cohort of HIV-1 controllers

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Title: Enrichment of HLA types and single-nucleotide polymorphism associated with non-progression in a strictly defined cohort of HIV-1 controllers
Authors: Westrop, SJ
Cocker, ATH
Boasso, A
Sullivan, AK
Nelson, MR
Imami, N
Item Type: Journal Article
Abstract: HIV-1 controllers (HIC) are extremely rare patients with the ability to control viral replication, maintain unchanging CD4 T-cell count, and evade disease progression for extensive periods of time, in the absence of antiretroviral therapy. In order to establish the representation of key genetic correlates of atypical disease progression within a cohort of HIV-1+ individuals who control viral replication, we examine four-digit resolution HLA type and single-nucleotide polymorphisms (SNP) previously identified to be correlated to non-progressive infection, in strictly defined HIC. Clinical histories were examined to identify patients exhibiting HIC status. Genomic DNA was extracted, and high definition HLA typing and genome-wide SNP analysis was performed. Data were compared with frequencies of SNP in European long-term non-progressors (LTNP) and primary infection cohorts. HLA-B alleles associated with atypical disease progression were at very high frequencies in the group of five HIC studied. All four HIC of European ancestry were HLA-B*57+ and half were also HLA-B*27+. All HIC, including one of self-reported African ethnicity, had the HLA-Cw*0602 allele, and the HLA-DQ9 allele was present only in HIC of European ancestry. A median 95% of the top 19 SNP known to be associated with LTNP status was observed in European HIC (range 78–100%); 17/19 of the SNP considered mapped to chromosome 6 in the HLA region, whereas 2/19 mapped to chromosome 8. The HIC investigated here demonstrated high enrichment of HLA types and SNP previously associated with long-term non-progression. These findings suggest that the extreme non-progressive phenotype considered here is associated with a genetic signature characterized by a single-genetic unit centered around the HLA-B*57 haplotype and the possible additive effect of HLA-B*27.
Issue Date: 27-Jun-2017
Date of Acceptance: 12-Jun-2017
URI: http://hdl.handle.net/10044/1/49144
DOI: https://dx.doi.org/10.3389/fimmu.2017.00746
ISSN: 1664-3224
Publisher: Frontiers Media
Journal / Book Title: Frontiers in Immunology
Volume: 8
Copyright Statement: © 2017 Westrop, Cocker, Boasso, Sullivan, Nelson and Imami. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publica- tion in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Sponsor/Funder: Westminster Medical School Research Trust
St Stephen's Aids Trust
Commission of the European Communities
Westminster Medical School Research Trust
St Stephen's Aids Trust
Medical Research Council
Funder's Grant Number: PhD Studentship
PhD Studentship top up
J R C 11 PhD 001
Keywords: Science & Technology
Life Sciences & Biomedicine
disease progression
elite controllers
HLA antigens
single-nucleotide polymorphism
Publication Status: Published
Article Number: ARTN 746
Appears in Collections:Department of Medicine (up to 2019)