Preferential CTL targeting of Gag is associated with relative viral control in long-term surviving HIV-1 infected former plasma donors from China |
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Authors: | Mingming Jia Kunxue Hong Jianping Chen Yuhua Ruan Zhe Wang Bing Su Guoliang Ren Xiaoqing Zhang Zhen Liu Quanbi Zhao Dan Li Hong Peng Marcus Altfeld Bruce D Walker Xu G Yu Yiming Shao |
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Affiliation: | 1.State Key Laboratory for Infectious Disease Prevention and Control, National Center for AIDS/STD Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China;2.Henan Center for Disease Control and Prevention, Zhengzhou, Henan 450016, China;3.Anhui Center for Disease Control and Prevention, Hefei, Anhui 230061, China;4.Ragon Institute of MGH, MIT, and Harvard, Charlestown, MA 02129, USA |
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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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Keywords: | human immunodeficiency virus type 1 cytotoxic T lymphocytes human leukocyte antigen class I Gag |
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