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Retrovirology:研究揭示宿主免疫细胞调控HIV-1感染的机制

2013-09-30 中科院生化与细胞所 中科院生化与细胞所

9月18日,Retrovirology在线发表了中科院上海生科院生物化学与细胞生物学研究所王红艳研究组的研究成果Immune adaptor ADAP in T cells regulates HIV-1 transcription and cell-cell viral spread via different co-receptors。该成果揭示了在HIV-1感染T细胞的过程中,免疫衔接蛋白A

9月18日,Retrovirology在线发表了中科院上海生科院生物化学与细胞生物学研究所王红艳研究组的研究成果Immune adaptor ADAP in T cells regulates HIV-1 transcription and cell-cell viral spread via different co-receptors。该成果揭示了在HIV-1感染T细胞的过程中,免疫衔接蛋白ADAP通过参与不同共刺激分子CD28或LFA-1的信号通路,分别调控HIV-1在T细胞内的转录、HIV-1在树突状细胞DC-T细胞之间的播散。

当T细胞受体(TCR)信号通路被激活后,ADAP与上游信号分子SLP76结合,构建TCR介导的inside-out信号通路,导致T细胞表面整合素(integrin)粘附能力增强,并促进T细胞活化。该研究发现:(1)在HIV-1感染的DC向未感染的T细胞播散病毒时,降低T细胞中ADAP的表达或阻止SLP76-ADAP信号复合体,通过抑制整合素LFA-1介导的病毒突触(Virological Synapse)的形成,进而阻止HIV-1在免疫细胞间的传播;(2)T细胞的活化能促进HIV-1的感染。当T细胞接受来自共刺激分子CD28的信号后,利用SLP76-ADAP信号复合体,活化转录因子NF-κB,促进HIV-1的转录。但此转录过程不依赖整合素LFA-1的活化。该研究从宿主免疫细胞的角度出发,首次揭示免疫衔接蛋白ADAP利用不同信号通路,多环节参与HIV-1转录、HIV-1在细胞间播散的感染过程。这项研究提示靶向宿主免疫细胞中的SLP76-ADAP信号复合体,可能作为控制HIV-1感染的新靶点。

该研究课题与英国剑桥大学Christopher E Rudd教授合作共同完成,并获得中科院上海巴斯德所王建华研究组的大力帮助。

该课题得到国家科技部、国家自然科学基金委、浦江人才计划和中国科学院分子病毒与免疫重点实验室的经费支持。 

原文阅读

Wei B, Han L, Abbink TE, Groppelli E, Lim D, Thaker YR, Gao W, Zhai R, Wang J, Lever A, Jolly C, Wang H, Rudd CE.Immune adaptor ADAP in T cells regulates HIV-1 transcription and cell-cell viral spread via different co-receptors.Retrovirology. 2013 Sep 18;10(1):101.

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    2014-04-05 ysjykql
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    2013-10-02 wincls

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