Co-operative additive effects between HLA alleles in control of HIV-1.
Co-operative additive effects between HLA alleles in control of HIV-1.
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DOI：
10.1371/journal.pone.0047799
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Goulder PJ
中科院分区：
文献类型：
--
作者：
Matthews PC;Listgarten J;Carlson JM;Payne R;Huang KH;Frater J;Goedhals D;Steyn D;van Vuuren C;Paioni P;Jooste P;Ogwu A;Shapiro R;Mncube Z;Ndung'u T;Walker BD;Heckerman D;Goulder PJ
HLA I类基因型是HIV感染结果的主要决定因素，某些等位基因对HIV疾病结果的影响已得到充分研究。最近的研究表明，某些处于连锁不平衡的HLA I类等位基因，如HLA-A*74和HLA-B*57，似乎协同作用，导致对HIV的免疫控制比单独由任一单个等位基因介导的更强。在这里，我们调查HLA等位基因的程度-不考虑连锁不平衡-功能合作。我们在这里改进了一种计算方法来分析>2000名感染C进化枝HIV的受试者，首先辨别每个等位基因对疾病控制的个体效应，其次识别介导“合作累加”效应的等位基因对，以改善疾病抑制或促进免疫失败。我们鉴定了六对HLA I类等位基因，它们在介导HIV疾病控制中具有协同加和效应，以及四对危险等位基因，它们一起出现，预测更糟糕的疾病结果（每种情况下q<0.05）。我们开发了一种新的“共享评分”来量化HIV蛋白质组中HLA等位基因对产生的CD 8 + T细胞应答的广度，并使用该评分来证明成功的病毒血症抑制与独特的CD 8 + T细胞应答的广度相关（p = 0.03）。 这些结果确定了HLA I类等位基因之间的合作效应，在一个扩展的南部非洲队列中控制HIV-1，并强调互补性和CD 8 + T细胞靶向的广度作为这种效应的一个潜在机制。
HLA class I genotype is a major determinant of the outcome of HIV infection, and the impact of certain alleles on HIV disease outcome is well studied. Recent studies have demonstrated that certain HLA class I alleles that are in linkage disequilibrium, such as HLA-A*74 and HLA-B*57, appear to function co-operatively to result in greater immune control of HIV than mediated by either single allele alone. We here investigate the extent to which HLA alleles - irrespective of linkage disequilibrium - function co-operatively. We here refined a computational approach to the analysis of >2000 subjects infected with C-clade HIV first to discern the individual effect of each allele on disease control, and second to identify pairs of alleles that mediate ‘co-operative additive’ effects, either to improve disease suppression or to contribute to immunological failure. We identified six pairs of HLA class I alleles that have a co-operative additive effect in mediating HIV disease control and four hazardous pairs of alleles that, occurring together, are predictive of worse disease outcomes (q<0.05 in each case). We developed a novel ‘sharing score’ to quantify the breadth of CD8+ T cell responses made by pairs of HLA alleles across the HIV proteome, and used this to demonstrate that successful viraemic suppression correlates with breadth of unique CD8+ T cell responses (p = 0.03). These results identify co-operative effects between HLA Class I alleles in the control of HIV-1 in an extended Southern African cohort, and underline complementarity and breadth of the CD8+ T cell targeting as one potential mechanism for this effect.
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影响因子：
6.7
作者：
Brumme ZL;Brumme CJ;Heckerman D;Korber BT;Daniels M;Carlson J;Kadie C;Bhattacharya T;Chui C;Szinger J;Mo T;Hogg RS;Montaner JS;Frahm N;Brander C;Walker BD;Harrigan PR
通讯作者：
Harrigan PR
影响因子：
56.9
作者：
Carrington, M;Nelson, GW;O'Brien, SJ
通讯作者：
O'Brien, SJ
DOI：
10.1084/jem.20072457
发表时间：
2008-05-12
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Goepfert PA;Lumm W;Farmer P;Matthews P;Prendergast A;Carlson JM;Derdeyn CA;Tang J;Kaslow RA;Bansal A;Yusim K;Heckerman D;Mulenga J;Allen S;Goulder PJ;Hunter E
通讯作者：
Hunter E
影响因子：
3.7
作者：
Carlson J;Kadie C;Mallal S;Heckerman D
通讯作者：
Heckerman D
影响因子：
1.2
作者：
Huang, Kuan-Hsiang Gary;Goedhals, Dominique;Frater, John
通讯作者：
Frater, John