Human immunodeficiency virus type 1 specific cytotoxic T lymphocyte responses in Chinese infected with HIV-1 B'/C Recombinant (CRF07_BC).

Human immunodeficiency virus type 1 specific cytotoxic T lymphocyte responses in Chinese infected with HIV-1 B'/C Recombinant (CRF07_BC).
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DOI:
10.1186/1742-4690-4-62
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发表时间:
2007-08-30
期刊:
影响因子:
3.3
通讯作者:
Shao, Yiming
Shao, Yiming
中科院分区:
医学2区
文献类型:
--
作者:
Chen, Jianping;Hong, Kunxue;Jia, Mingming;Liu, Hongwei;Zhang, Yuanzhi;Liu, Sha;Zhang, Xiaoqing;Zhao, Hongjing;Peng, Hong;Ma, Pengfei;Xing, Hui;Ruan, Yuhua;Williams, Katie L.;Yu, Xu G.;Altfeld, Marcus;Walker, Bruce D.;Shao, Yiming

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在当地流行的HIV-1毒株感染的人群中,HIV-1特异性T细胞反应的特征将促进HIV-1疫苗的开发。从中国新疆招募60名静脉注射吸毒者感染HIV-1循环重组型07_BC (CRF07_BC),该病毒已在中国西部从北向南迅速传播,研究了覆盖整个一致进化支B和C蛋白质组的重叠肽(OLP)在单肽水平上对HIV-1特异性T细胞的反应。CTL应答识别的OLPs的总大小和总数的中位数分别为10925 SFC/百万PBMC和25 OLPs,而clade C肽的中位数明显高于clade B肽的中位数。免疫优势区占HIV-1蛋白质组的14%(58/413),除Tat、Vpu和Pol-PR外,广泛分布于整个HIV-1蛋白质组中,Gag、Pol-RT、Pol-Int和Nef是最常见的靶向区域。亚显性表位主要位于p24、Nef、整合酶、Vpr和Vif。在针对C枝OLPs的响应中,61.75%(972/1574)的响应在对应的B枝OLPs测试中可以观察到。而Pol-PR和Vpu更倾向于靶向B支序列而不是C支序列,这与CRF07_BC的重组模式是一致的。与CD4细胞计数小于200/mm3或大于400/mm3的受试者相比,CD4细胞计数在200至400/mm3之间的受试者观察到更强和更广泛的CTL反应,尽管没有发现累积CTL反应或总体宽度与CD4细胞计数或血浆病毒载量之间的显著相关性。这是第一个全面研究中国HIV-1 CRF07_BC感染者的T细胞反应的研究,其中观察到交叉反应性的细微差异,尽管在B支感染人群中显示了相似的总体免疫反应模式。在这一人群中发现的免疫优势区可以促进中国未来HIV-1疫苗的开发。
The characterization of HIV-1-specific T cell responses in people infected with locally circulating HIV-1 strain will facilitate the development of HIV-1 vaccine. Sixty intravenous drug users infected with HIV-1 circulating recombinant form 07_BC (CRF07_BC), which has been spreading rapidly in western China from north to south, were recruited from Xinjiang, China to assess the HIV-1-specific T cell responses at single peptide level with overlapping peptides (OLP) covering the whole concensus clades B and C proteome. The median of the total magnitude and total number of OLPs recognized by CTL responses were 10925 SFC/million PBMC and 25 OLPs, respectively, when tested by clade C peptides, which was significantly higher than when tested by clade B peptides. The immunodominant regions, which cover 14% (58/413) of the HIV-1 proteome, are widely distributed throughout the HIV-1 proteome except in Tat, Vpu and Pol-PR, with Gag, Pol-RT, Pol-Int and Nef being most frequently targeted. The subdominant epitopes are mostly located in p24, Nef, integrase, Vpr and Vif. Of the responses directed to clade C OLPs, 61.75% (972/1574) can be observed when tested with corresponding clade B OLPs. However, Pol-PR and Vpu tend to be targeted in the clade B sequence rather than the clade C sequence, which is in line with the recombinant pattern of CRF07_BC. Stronger and broader CTL responses in subjects with CD4 cell counts ranging from 200 to 400/mm3 were observed when compared to those with less than 200/mm3 or more than 400/mm3, though there have been no significant correlations identified between the accumulative CTL responses or overall breadth and CD4 cell count or plasma viral load. This is the first study conducted to comprehensively address T cell responses in Chinese subjects infected with HIV-1 CRF07_BC in which subtle differences in cross-reactivity were observed, though similar patterns of overall immune responses were demonstrated with clade B infected populations. The immunodominant regions identified in this population can facilitate future HIV-1 vaccine development in China.
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发表时间: 1999-11-01
影响因子: 15.9
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DOI: 10.1038/nm0297-212
发表时间: 1997-02-01
期刊: NATURE MEDICINE
影响因子: 82.9
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通讯作者: RowlandJones, S