趋化因子受体4（CXCR4）嗜亲性HIV-1 gp120对基质细胞衍生因子-1α（SDF-1α）诱导的趋化作用的抑制需要淋巴细胞特异性蛋白酪氨酸激酶（Lck），并与丝切蛋白磷酸化相关。

CXCR4 Tropic HIV-1 gp120 Inhibition of SDF-1α-Induced Chemotaxis Requires Lck and is Associated with Cofilin Phosphorylation.

作者信息

Trushin Sergey A, Bren Gary D, Badley Andrew D

机构信息

Division of Infectious Diseases, Mayo Clinic, Rochester, MN 55905, USA.

出版信息

Open Virol J. 2010 Jun 23;4:157-62. doi: 10.2174/1874357901004010157.

OBJECTIVE

HIV gp120 is a pleiotropic protein present in the plasma and tissues of HIV-infected patients, which affects a variety of homeostatic functions. In this report, we examine the mechanism of how gp120 blocks CD4 T cells from migrating towards SDF-1α.

METHODS

In vitro treatment of primary CD4 T cells with CXCR4 tropic gp120, SDF, and measurement of chemotaxis and cell signaling.

RESULTS

gp120 signaling through CD4 receptor and Lck are required for its ability to inhibit chemotaxis induced by SDF, as demonstrated by CD4 receptor decoys, Lck inhibitors, as well as cells deficient in Lck, in which Lck expression is restored. Blocking Lck abrogates the ability of CXCR4 tropic gp120 to antagonize SDF-1α-induced chemotaxis. This inhibition is associated with cofilin phosphorylation, thereby providing a potential mechanism.

CONCLUSION

We conclude that the ability of gp120 to inhibit SDF-1α-induced chemotaxis is mediated by the CD4 receptor and Lck signaling, potentially by promoting cofilin phosphorylation.

目的

HIV gp120是一种存在于HIV感染患者血浆和组织中的多效性蛋白，它会影响多种稳态功能。在本报告中，我们研究了gp120阻止CD4 T细胞向基质细胞衍生因子1α（SDF-1α）迁移的机制。

方法

用趋化因子受体4（CXCR4）嗜性gp120、SDF对原代CD4 T细胞进行体外处理，并检测趋化性和细胞信号传导。

结果

通过CD4受体和淋巴细胞特异性蛋白酪氨酸激酶（Lck）的gp120信号传导是其抑制SDF诱导趋化性能力所必需的，这一点由CD4受体诱饵、Lck抑制剂以及Lck缺陷但Lck表达得以恢复的细胞所证明。阻断Lck可消除CXCR4嗜性gp120拮抗SDF-1α诱导趋化性的能力。这种抑制作用与丝切蛋白磷酸化有关，从而提供了一种潜在机制。