High frequency of HIV mutations associated with HLA-C suggests enhanced HLA-C-restricted CTL selective pressure associated with an AIDS-protective polymorphism.
High frequency of HIV mutations associated with HLA-C suggests enhanced HLA-C-restricted CTL selective pressure associated with an AIDS-protective polymorphism.
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DOI：
10.4049/jimmunol.1103472
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发表时间：
2012-05-01
期刊：
影响因子：
--
通讯作者：
Rowland-Jones SL
中科院分区：
文献类型：
--
作者：
Blais ME;Zhang Y;Rostron T;Griffin H;Taylor S;Xu K;Yan H;Wu H;James I;John M;Dong T;Rowland-Jones SL
延迟的HIV-1疾病进展与HLA-C基因上游的单核苷酸多态性相关，该多态性与HLA-C抗原的差异表达相关。这种多态性最近被证明是HLA-C的3′UTR中的保护性变体的标记，该保护性变体破坏了microRNA结合位点，导致细胞表面HLA-C表达增强。具有“高”HLA-C表达的个体是否表现出比其对应者更强的HLA-C限制性免疫应答，从而产生更好的病毒控制尚未确定。我们假设HLA-C限制性免疫压力在HLA-C等位基因高表达的受试者中会更大。使用来自中国独特的窄源流行的队列，我们鉴定了HIV前病毒DNA中与HLA-C完全相关的突变，这些突变被用作对病毒施加的免疫压力强度的标记。我们发现在具有高表达HLA-C等位基因的个体中突变频率增加，这也与HLA-C限制性CD 8 + T细胞产生IFN-γ相关。这些发现表明，在具有保护性基因型的受试者中，对HIV的免疫压力更强，并突出了HLA-C限制性反应在HIV控制中的潜在作用。这是第一个体内证据支持在HIV感染期间非高加索人中HLA-C限制性反应的保护作用。
Delayed HIV-1 disease progression is associated with a single nucleotide polymorphism upstream of the HLA-C gene that correlates with differential expression of the HLA-C antigen. This polymorphism was recently shown to be a marker for a protective variant in the 3′UTR of HLA-C that disrupts a microRNA binding site, resulting in enhanced HLA-C expression at the cell surface. Whether individuals with ‘high’ HLA-C expression show a stronger HLA-C-restricted immune response exerting better viral control than that of their counterparts has not been established. We hypothesised that the magnitude of the HLA-C-restricted immune pressure on HIV would be greater in subjects with highly expressed HLA-C alleles. Using a cohort derived from a unique narrow source epidemic in China, we identified mutations in HIV proviral DNA exclusively associated with HLA-C which were used as markers for the intensity of the immune pressure exerted on the virus. We found an increased frequency of mutations in individuals with highly expressed HLA-C alleles which also correlated with IFN-γ production by HLA-C-restricted CD8+ T-cells. These findings show that immune pressure on HIV is stronger in subjects with the protective genotype and highlights the potential role of HLA-C-restricted responses in HIV control. This is the first in vivo evidence supporting the protective role of HLA-C-restricted responses in non-Caucasians during HIV infection.
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影响因子：
3.8
作者：
Shrestha, Sadeep;Aissani, Brahim;Tang, Jianming
通讯作者：
Tang, Jianming
影响因子：
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影响因子：
13.5
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通讯作者：
Gaudieri, Silvana
影响因子：
3.7
作者：
Buranapraditkun S;Hempel U;Pitakpolrat P;Allgaier RL;Thantivorasit P;Lorenzen SI;Sirivichayakul S;Hildebrand WH;Altfeld M;Brander C;Walker BD;Phanuphak P;Hansasuta P;Rowland-Jones SL;Allen TM;Ruxrungtham K
通讯作者：
Ruxrungtham K
影响因子：
5.4
作者：
Makadzange, Azure T.;Gillespie, Geraldine;Rowland-Jones, Sarah L.
通讯作者：
Rowland-Jones, Sarah L.