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尽管存在较高程度的基因多样性,但在原发性HIV-1感染中,HIV-1 Nef优先被CD8 T细胞识别。

HIV-1 Nef is preferentially recognized by CD8 T cells in primary HIV-1 infection despite a relatively high degree of genetic diversity.

作者信息

Lichterfeld Mathias, Yu Xu G, Cohen Daniel, Addo Marylyn M, Malenfant Jessica, Perkins Beth, Pae Eunice, Johnston Mary N, Strick Daryld, Allen Todd M, Rosenberg Eric S, Korber Bette, Walker Bruce D, Altfeld Marcus

机构信息

Partners AIDS Research Center and Howard Hughes Medical Institute, Massachusetts General Hospital and Division of AIDS, Harvard Medical School, Boston, Massachusetts 02129, USA.

出版信息

AIDS. 2004 Jul 2;18(10):1383-92. doi: 10.1097/01.aids.0000131329.51633.a3.

Abstract

OBJECTIVE

To compare the magnitude, breadth and protein specificity of HIV-1-specific CD8 T-cell responses against the clade B consensus sequence during primary and chronic HIV-1 infection and to analyze the impact of viral diversity on the localization of detected responses.

METHODS

HIV-1-specific CD8 T-cell responses against the clade B consensus sequence in individuals with acute (n = 10), early (n = 19) and chronic (n = 10) infection were longitudinally assessed using an interferon-gamma EliSpot assay.

RESULTS

CD8 T-cell responses against clade B consensus sequences were preferentially directed against central regions of Nef during primary HIV-1 infection, despite a relatively higher degree of genetic diversity compared with other subsequently targeted regions. In subjects with acute and early infection, Nef-specific CD8 T-cell responses against the consensus Nef sequence represented 94 and 46% of the total magnitude of HIV-1-specific CD8 T-cell responses, respectively. Subjects with untreated chronic infection exhibited broadly diversified CD8 T-cell responses against more conserved viral regions, with only 17% of virus-specific T-cell responses targeting Nef. The initial immunodominance of Nef persisted in individuals with treated acute infection, but shifted rapidly to Gag, Env and Pol in subjects with continuous antigen exposure.

CONCLUSION

These data show that despite relatively high sequence variability, viral regions within the clade B consensus sequence of Nef are preferentially recognized during primary HIV-1 infection. Later diversification of responses to other proteins during prolonged antigen exposure provides evidence of the initial preferential immunogenicity of Nef epitopes compared to similarly conserved regions within other viral proteins.

摘要

目的

比较在原发性和慢性HIV-1感染期间,针对B亚型共识序列的HIV-1特异性CD8 T细胞反应的强度、广度和蛋白质特异性,并分析病毒多样性对检测到的反应定位的影响。

方法

使用干扰素-γ酶联免疫斑点试验纵向评估急性感染(n = 10)、早期感染(n = 19)和慢性感染(n = 10)个体中针对B亚型共识序列的HIV-1特异性CD8 T细胞反应。

结果

在原发性HIV-1感染期间,针对B亚型共识序列的CD8 T细胞反应优先针对Nef的中央区域,尽管与其他随后靶向的区域相比,其遗传多样性程度相对较高。在急性和早期感染的受试者中,针对共识Nef序列的Nef特异性CD8 T细胞反应分别占HIV-1特异性CD8 T细胞反应总量的94%和46%。未经治疗的慢性感染受试者表现出针对更保守病毒区域的广泛多样化CD8 T细胞反应,只有17%的病毒特异性T细胞反应靶向Nef。在接受治疗的急性感染个体中,Nef最初的免疫优势持续存在,但在持续抗原暴露的受试者中迅速转移到Gag、Env和Pol。

结论

这些数据表明,尽管序列变异性相对较高,但在原发性HIV-1感染期间,Nef的B亚型共识序列内的病毒区域仍被优先识别。在长期抗原暴露期间对其他蛋白质的反应后期多样化提供了证据,表明与其他病毒蛋白内的类似保守区域相比,Nef表位最初具有优先免疫原性。

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