Abstract
It is generally believed that CD8+ cytotoxic T lymphocytes (CTLs) play a critical role in limiting the replication of human immunodeficiency virus type 1 (HIV-1) and in determining the outcome of the infection, and this effect may partly depend on which HIV product is preferentially targeted. To address the correlation between HIV-1-specific CTL responses and virus replication in a cohort of former plasma donors (FPDs), 143 antiretroviral therapy naive FPDs infected with HIV-1 clade B' strains were assessed for HIV-1-specific CTL responses with an IFN-γ Elispot assay at single peptide level by using overlapping peptides (OLPs) covering the whole consensus clade B proteome. By using a Spearman's rank correlation analysis, we found that the proportion of Gag-specific CTL responses among the total virus-specific CTL activity was inversely correlated with viral loads while being positively correlated to CD4 counts, as opposed to Pol- and Env-specific responses that were associated with increased viral loads and decreased CD4 counts. In addition, Vpr-specifc CTL responses showed a similar protective effect with Gag responses, but with a much lower frequency of recognition. Significantly, we also observed an association between HLA-A*30/B*13/Cw*06 haplotype and lower viral loads that was probably due to restricted Gag-specific CTL responses. Thus, our data demonstrate the prominent role of Gag-specific CTL responses in disease control. The advantage of HLA-A*30/B*13/Cw*06 haplotype in viral control may be associated with the contribution of Gag-specific CTL responses in the studied individuals.
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Acknowledgements
This project has been funded in part by the National Institute of Allergy and Infectious Disease, National Institutes of Health (N01-AI-30024), the China Mega-Project for Infectious Disease (2008ZX10001-010), International Cooperation in Science and Technology from the Chinese Ministry of Science and Technology (2006DFA31510) and the National Nature Science Foundation of China (81172809, 81020108030). We thank Rebecca Armstrong for critical reading of the manuscript.
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( Supplementary information is linked to the online version of the paper on the Cell Research website.)
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Supplementary information, Table S1
Correlations between HIV-1 specific CTL responses and disease progression. (PDF 70 kb)
Supplementary information, Table S2
CTL responses against HIV-1 proteins of 14 elite controllers and 17 AIDS patients (PDF 69 kb)
Supplementary information, Figure S1
Correlation of the magnitude and contribution of HIV-1-specific CTL response with CD4 counts. (PDF 70 kb)
Supplementary information, Figure S2
Correlation of the breadth and contribution of HIV-1-specific CTL response with CD4 counts. (PDF 68 kb)
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Jia, M., Hong, K., Chen, J. et al. Preferential CTL targeting of Gag is associated with relative viral control in long-term surviving HIV-1 infected former plasma donors from China. Cell Res 22, 903–914 (2012). https://doi.org/10.1038/cr.2012.19
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DOI: https://doi.org/10.1038/cr.2012.19
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