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This article is part of the supplement: AIDS Vaccine 2012

Open Access Poster presentation

The HIV-1 protective -35SNP effect in Caucasians is CD8 T cell mediated

T Corrah1*, S Brackenridge2, N Goonetilleke2, H Yang2, S Deeks3, L Dorrell2, M Cohen4 and A McMichael2

  • * Corresponding author: T Corrah

Author Affiliations

1 Addenbrooks Hospital, University of Cambridge, Cambridge, UK

2 Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK

3 University of California San Francisco, San Francisco, CA, USA

4 University of North Carolina School of Medicine, NC, USA

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Retrovirology 2012, 9(Suppl 2):P281  doi:10.1186/1742-4690-9-S2-P281

The electronic version of this article is the complete one and can be found online at: http://www.retrovirology.com/content/9/S2/P281


Published:13 September 2012

© 2012 Corrah et al; licensee BioMed Central Ltd.

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Background

Previous studies in Caucasians have observed that a single nucleotide polymorphism 35kb upstream of the HLA-C gene (-35SNP) associates with control of HIV-1 viral load set-point and cell surface expression of HLA-C. HIV-1 selectively downregulates HLA-A and HLA-B but not HLA-C, via the action of the Nef protein. Thus it has been speculated that higher cell surface HLA-C expression results in a stronger HLA-C-restricted T cell response which might play a role in the control of HIV-1 replication in individuals with the protective -35C variant. However, HLA-C-restricted CD8 T cell responses are relatively weak and we could find no difference in functional HLA-C-restricted CD8 T cell activity measured by IFN-γ ELISPOT assay, according to -35SNP genotype. Therefore, we aimed to examine if there is any correlation between total CD8 T cell function and the -35SNP.

Methods

The viral suppression assay, which involves directly infecting autologous CD4 T cells with primary HIV-1 strains and co-culturing with autologous CD8 T cells, was used as a surrogate for immune control in vivo. The CD8 T cells from 46 antiretroviral therapy naïve HIV-1 infected Caucasians were assessed using this assay.

Results

When CD8 T cell antiviral activity was grouped according to -35SNP genotype, the -35CC group possessed significantly higher CD8 T cell antiviral activity than the -35TT group (p=0.0151; Mann-Whitney). Protective HLA-B alleles were always in linkage disequilibrium with HLA-C alleles that are in linkage disequilibrium with the -35C allele. Similarly risk HLA-B alleles were in linkage disequilibrium with HLA-C alleles that are in linkage disequilibrium with the -35T allele.

Conclusion

In conclusion, the protective -35SNP effect in HIV-1 disease is mediated through CD8 T cells. However, the -35SNP may simply be a marker for protective and risk HLA-B alleles.