Preferential CTL targeting of Gag is associated with relative viral control in long-term surviving HIV-1 infected former plasma donors from China
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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Gag 的优先 CTL 靶向与长期存活的 HIV-1 感染的中国前血浆捐献者的相对病毒控制相关
DOI：
10.1038/cr.2012.19
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发表时间：
2012-05-01
期刊：
影响因子：
44.1
通讯作者：
Shao, Yiming
中科院分区：
文献类型：
--
作者：
Jia, Mingming;Hong, Kunxue;Shao, Yiming
一般认为，CD 8+细胞毒性T淋巴细胞（CTL）在限制人类免疫缺陷病毒1型（HIV-1）的复制和确定感染的结果中起着关键作用，这种作用可能部分取决于HIV产品的优先目标。为了研究HIV-1特异性CTL应答与前血浆供体（FPD）中病毒复制之间的相关性，使用覆盖整个共有进化枝B蛋白质组的重叠肽（OLP），在单肽水平上用IFN-γ Elispot测定法评估了143名感染HIV-1进化枝B '株的抗逆转录病毒治疗初治FPD的HIV-1特异性CTL应答。通过使用斯皮尔曼等级相关分析，我们发现，总病毒特异性CTL活性中的GAG特异性CTL应答的比例与病毒载量呈负相关，而与CD 4计数呈正相关，而与病毒载量增加和CD 4计数减少相关的Pol-Env特异性应答相反。此外，Vpr特异性CTL应答显示出与Gag应答相似的保护作用，但识别频率低得多。值得注意的是，我们还观察到HLA-A* 30/B* 13/Cw* 06单倍型和较低的病毒载量之间的关联，这可能是由于限制性的GAG特异性CTL应答。因此，我们的数据表明，在疾病控制中的重要作用的GAG特异性CTL反应。HLA-A* 30/B* 13/Cw* 06单倍型在病毒控制中的优势可能与所研究个体中的GAG特异性CTL应答的贡献有关。
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.