HIV-1包膜蛋白可诱导原代人CD4(+) T细胞中半胱天冬酶-3的激活和粘着斑激酶的裂解。
HIV-1 envelope induces activation of caspase-3 and cleavage of focal adhesion kinase in primary human CD4(+) T cells.
作者信息
Cicala C, Arthos J, Rubbert A, Selig S, Wildt K, Cohen O J, Fauci A S
机构信息
Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
出版信息
Proc Natl Acad Sci U S A. 2000 Feb 1;97(3):1178-83. doi: 10.1073/pnas.97.3.1178.
Binding of HIV type 1 (HIV-1) envelope glycoproteins to the surface of a CD4(+) T cell transduces intracellular signals through the primary envelope receptor, CD4, and a coreceptor, either CCR5 or CXCR4. Furthermore, envelope-CD4(+) cell interactions increase rates of apoptosis in peripheral blood mononuclear cells (PBMCs). We demonstrate that in primary T lymphocytes, recombinant HIV-1 envelope proteins induce the activation of caspase-3 and caspase-6, which belong to a family of cysteine proteases that, upon activation, promote programmed cell death. Envelope-mediated activation of caspase-3 and caspase-6 depended on envelope-CD4 receptor interactions; CCR5-utilizing as well as CXCR4-utilizing envelopes elicited this response. Focal adhesion kinase (FAK) is a substrate of both caspase-3 and caspase-6, and inactivation of FAK by these caspases promotes apoptosis. En-velope treatment of lymphocytes led to the cleavage of FAK in a manner consistent with caspase-mediated cleavage.
1型人类免疫缺陷病毒（HIV-1）包膜糖蛋白与CD4(+) T细胞表面结合，通过主要包膜受体CD4和共受体CCR5或CXCR4转导细胞内信号。此外，包膜与CD4(+) 细胞的相互作用会增加外周血单核细胞（PBMC）的凋亡率。我们证明，在原代T淋巴细胞中，重组HIV-1包膜蛋白可诱导半胱天冬酶-3和半胱天冬酶-6的激活，这两种酶属于半胱氨酸蛋白酶家族，激活后会促进程序性细胞死亡。包膜介导的半胱天冬酶-3和半胱天冬酶-6的激活依赖于包膜与CD4受体的相互作用；利用CCR5以及利用CXCR4的包膜均可引发这种反应。粘着斑激酶（FAK）是半胱天冬酶-3和半胱天冬酶-6的底物，这些半胱天冬酶使FAK失活会促进细胞凋亡。用包膜处理淋巴细胞会导致FAK的裂解，其方式与半胱天冬酶介导的裂解一致。
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