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JBC:新研究揭示艾滋病毒感染辅助性T细胞机制

来源:生物谷 2012-09-27 15:09

2012年9月27日 电 /生物谷BIOON/ --近日,一项发表在Journal of Biological Chemistry杂志上的研究揭示了艾滋病毒是如何感染帮助人体免疫系统进行抗感染的辅助性T细胞。该研究由Mason国家生物防御和感染性疾病中心教授Yuntao Wu领导完成。

HIV病毒劫持辅助性T细胞,当辅助性T细胞数量直线下降时,身体容易患病。但并非所有的辅助性T细胞都是一样的,有些辅助性T细胞“经验丰富”,被称为记忆辅助性T细胞,有些辅助性T细胞属于幼稚型细胞或“处女”细胞,这些细胞不能有效应对感染。

Mason研究人员研究了为什么HIV优先感染辅助性T细胞,而不是其他类型的T细胞。Weifeng Wang说在艾滋病患者体内的人类免疫力缺乏病毒(HIV)主要能杀死大多数记忆性T细胞。

我们想探寻是什么原因导致记忆性T细胞和幼稚型T细胞在分子水平上存在了差异。哈佛医学院Dana-Farber癌症研究所研究员Wang说与未成熟的辅助性T细胞不同,记忆性T细胞的能动性更强,这会吸引住HIV病毒使得记忆性T细胞更加脆弱。

Wu说:细胞骨架的作用就像肌肉,细胞骨架主要推动细胞迁移。在过去的一年中,我们已经研究出HIV是如何感染那些记忆性T细胞的。HIV要想感染这些细胞就必须穿越细胞骨架障碍。但多年来,我们并不知道病毒是如何穿越这样骨架结构的。

在这项最新研究中,研究人员发现HIV病毒利用受体附着细胞然后慢慢移动进入细胞内部。当这种病毒​​接触利用受体接触细胞时就是像有人按门铃那样,触发一个信号,门后就有人出来敞开了大门。

Wang说防治艾滋病毒研究应该从病毒本身出发,癌细胞和艾滋病毒感染宿主细胞之间有某些共同点比如都发生迁移,因此用于减缓癌细胞迁移的药物或许也可用于治疗艾滋病毒。(生物谷:Bioon.com)

A dichotomy in cortical actin and chemotactic actin activity between human memory and naive T cells contributes to their differential susceptibility to HIV-1 infection

Weifeng Wang, Jia Guo, Dongyang Yu1, Paul J. Vorster, WanJun Chen4 and Yuntao Wu*

Human memory and naive CD4 T cells can mainly be identified by the reciprocal expression of the CD45RO or CD45RA isoforms. In HIV-1 infection, blood CD45RO memory CD4 T cells are preferentially infected and serve as a major viral reservoir. The molecular mechanism dictating this differential susceptibility to HIV-1 remains largely obscure. Here, we report that the different susceptibility of memory and naive T cells to HIV is not determined by restriction factors such as Apobec3G or BST2. However, we observed a phenotypic distinction between human CD45RO and CD45RA resting CD4 T cells in their cortical actin density and actin dynamics. CD45RO CD4 T cells possess a higher cortical actin density and can be distinguished as CD45RO+/Actin/high. In contrast, CD45RA T cells are phenotypically CD45RA+/Actin/low. In addition, the cortical actin in CD45RO memory CD4 T cells is more dynamic and can respond to low dosages of chemotactic induction by SDF-1, whereas that of naive cells cannot, despite a similar level of the chemokine receptor CXCR4 present on both cells. We further demonstrate that this difference in the cortical actin contributes to their differential susceptibility to HIV-1; resting memory but not naive T cells are highly responsive to HIV-mediated actin dynamics which promote higher levels of viral entry and early DNA synthesis in resting memory CD4 T cells. Furthermore, transient induction of actin dynamics in resting naive T cells rescues HIV latent infection following CD3/CD28 stimulation. These results suggest a key role of chemotactic actin activity in facilitating HIV-1 latent infection of these T cell subsets. 

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