JBC：发现不同CD4 T细胞对HIV感染敏感性差异机制

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众说周知，HIV感染CD4 T细胞来摧毁机体的免疫系统，但不同的CD4 T细胞对HIV感染敏感性差异较大，但其机制却不为人知。近日，一项发表在Journal of Biological Chemistry杂志上的研究揭示了这一机制。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。

在HIV感染时，血液中的记忆性T细胞最易受到感染，而初始T细胞却不被感染。研究人员从分子水平上探寻是什么原因导致记忆性T细胞和初始T细胞对HIV感染敏感性存在了差异。结果发现这两种细胞的皮质肌动蛋白密度和肌动蛋白动力学特性存在很大差异，进一步发现这一差异正是导致其对HIV感染敏感性的原因。记忆性T细胞具有高密度的皮质肌动蛋白，而且其肌动蛋白的组装和解聚更快，从而促进病毒的进入和早期的DNA合成。




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.

原文链接http://www.jbc.org/content/287/42/35455