Determinants of human immunodeficiency virus type 1 escape from the primary CD8+ cytotoxic T lymphocyte response.
Determinants of human immunodeficiency virus type 1 escape from the primary CD8+ cytotoxic T lymphocyte response.
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DOI：
10.1084/jem.20040511
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发表时间：
2004-11-15
期刊：
影响因子：
--
通讯作者：
Borrow P
中科院分区：
文献类型：
--
作者：
Jones NA;Wei X;Flower DR;Wong M;Michor F;Saag MS;Hahn BH;Nowak MA;Shaw GM;Borrow P
CD 8+细胞毒性T淋巴细胞（CTL）在原发性人类免疫缺陷病毒（HIV）感染中对抑制病毒复制起重要作用。艾滋病毒的能力突变，以逃避CTL的压力越来越多地认识到，但从原发性艾滋病毒感染的CD 8 T细胞反应逃逸的全面研究目前缺乏。在这里，我们已经充分的特点，自体病毒Env，Gag，和达特蛋白在三个病人的主要CTL反应，并调查的程度，动力学和机制的病毒逃逸表位特异性成分的反应。在所有三个人中，我们观察到的变化开始在几个星期内感染的表位在病毒准种，这赋予逃逸的机制，包括改变肽呈递/识别和改变抗原处理的含位点。表现出早期CTL逃逸证据的含表位区域的数量范围从有效控制病毒复制的受试者中的21个中的1个到不能有效控制病毒复制的受试者中的7个中的5个。对HIV-1从>40种不同表位特异性CD 8 T细胞应答逃逸的程度和动力学的评估使得能够分析决定逃逸的因素，并表明逃逸受到内在病毒适应性的成本和CTL介导的对病毒复制的压力的广泛共显性分布的限制。
CD8+ cytotoxic T lymphocytes (CTLs) play an important role in containment of virus replication in primary human immunodeficiency virus (HIV) infection. HIV's ability to mutate to escape from CTL pressure is increasingly recognized; but comprehensive studies of escape from the CD8 T cell response in primary HIV infection are currently lacking. Here, we have fully characterized the primary CTL response to autologous virus Env, Gag, and Tat proteins in three patients, and investigated the extent, kinetics, and mechanisms of viral escape from epitope-specific components of the response. In all three individuals, we observed variation beginning within weeks of infection at epitope-containing sites in the viral quasispecies, which conferred escape by mechanisms including altered peptide presentation/recognition and altered antigen processing. The number of epitope-containing regions exhibiting evidence of early CTL escape ranged from 1 out of 21 in a subject who controlled viral replication effectively to 5 out of 7 in a subject who did not. Evaluation of the extent and kinetics of HIV-1 escape from >40 different epitope-specific CD8 T cell responses enabled analysis of factors determining escape and suggested that escape is restricted by costs to intrinsic viral fitness and by broad, codominant distribution of CTL-mediated pressure on viral replication.
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HIV-1 GAG中的簇突变是逃避HLA-B27限制的细胞毒性T淋巴细胞反应所必需的。
影响因子：
15.3
作者：
Kelleher, A D;Long, C;Holmes, E C;Allen, R L;Wilson, J;Conlon, C;Workman, C;Shaunak, S;Olson, K;Goulder, P;Brander, C;Ogg, G;Sullivan, J S;Dyer, W;Jones, I;McMichael, A J;Rowland-Jones, S;Phillips, R E
通讯作者：
Phillips, R E
影响因子：
5.4
作者：
Geels, MJ;Cornelissen, M;Goudsmit, J
通讯作者：
Goudsmit, J
DOI：
10.1073/pnas.93.26.15323
发表时间：
1996-12-24
影响因子：
11.1
作者：
Klenerman, P;Phillips, RE;Nowak, MA
通讯作者：
Nowak, MA
影响因子：
82.9
作者：
Goh, WC;Rogel, ME;Emerman, M
通讯作者：
Emerman, M
影响因子：
158.5
作者：
CLARK, SJ;SAAG, MS;SHAW, GM
通讯作者：
SHAW, GM