Preferential CTL targeting of Gag is associated with relative viral control in long-term surviving HIV-1 infected former plasma donors from China

• Published in: Cell research 2012-05, Vol.22 (5), p.903-914
• Main Authors: Jia, Mingming, Hong, Kunxue, Chen, Jianping, Ruan, Yuhua, Wang, Zhe, Su, Bing, Ren, Guoliang, Zhang, Xiaoqing, Liu, Zhen, Zhao, Quanbi, Li, Dan, Peng, Hong, Altfeld, Marcus, Walker, Bruce D, Yu, Xu G, Shao, Yiming
• Format: Article
• Language: English
• Subjects: 631/208/325/2483; 631/250/1933; 631/250/255/1901; Adult; Aged; Amino Acid Sequence; Anti-HIV Agents - therapeutic use; Antiretroviral agents; antiretroviral therapy; Biomedical and Life Sciences; Blood Donors; CD4 antigen; CD4 Lymphocyte Count; CD8 antigen; Cell Biology; China; Cohort Studies; Correlation analysis; CTL; Cytotoxicity; Data processing; Disease control; Enzyme-linked immunosorbent assay; Enzyme-Linked Immunospot Assay; Female; gag Gene Products, Human Immunodeficiency Virus - antagonists & inhibitors; gag Gene Products, Human Immunodeficiency Virus - metabolism; Gag protein; gamma -Interferon; Haplotypes; Histocompatibility antigen HLA; HIV Infections - drug therapy; HIV Infections - metabolism; HIV Infections - virology; HIV-1; HIV-1 - metabolism; HLA-A Antigens - immunology; HLA-B13 Antigen - immunology; HLA-C Antigens - immunology; Human immunodeficiency virus 1; Humans; Infection; Interferon-gamma - metabolism; Life Sciences; Lymphocytes; Lymphocytes T; Male; Middle Aged; Molecular Sequence Data; Original; original-article; Peptides; Peptides - chemistry; Peptides - metabolism; Replication; T-Lymphocytes, Cytotoxic - immunology; T-Lymphocytes, Cytotoxic - metabolism; Viral Load; 人类免疫缺陷病毒; 感染; 疾病控制; 细胞毒性T淋巴细胞; 血浆; 长期存活
• ISSN: 1001-0602; 1748-7838
• DOI: 10.1038/cr.2012.19

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-l-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-l-specific CTL responses with an IFN-γ Elispot as- say 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-speeific 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.