Alternate receptor usage of neuropilin-1 and glucose transporter protein 1 by the human T cell leukemia virus type 1
Alternate receptor usage of neuropilin-1 and glucose transporter protein 1 by the human T cell leukemia virus type 1
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人类 T 细胞白血病病毒 1 型对 Neuropilin-1 和葡萄糖转运蛋白 1 的替代受体使用
DOI：
10.1016/j.virol.2009.10.015
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发表时间：
2010-01-20
期刊：
影响因子：
3.7
通讯作者：
Alkhatib, Ghalib
中科院分区：
文献类型：
--
作者：
Jin, Qingwen;Alkhatib, Bashar;Alkhatib, Ghalib
最近的研究表明，神经菌素-1(NP-1)参与了HTLV-1的进入，然而，NP-1在这一过程中所起的作用尚不清楚。我们证明了人NP-1的异位表达而不是NP-2的表达增加了对HTLV-1的易感性。SiRNA介导的NP-1表达抑制与HTLV-1Env介导的融合显著减少相关。血管内皮生长因子(VEGF165)可下调U87细胞表面NP-1的表达，抑制HTLV-1感染。而VEGF(165)对原代星形胶质细胞的感染有部分抑制作用，对HeLa细胞的感染无明显影响。血管内皮生长因子(165)和葡萄糖转运蛋白1抗体(抗GLUT-1)均可阻断原代星形胶质细胞的感染，但只有抗GLUT-1抗体足以阻断HeLa细胞的感染。HTLV-1Env在原代培养的人星形胶质细胞中与NP-1和GLUT-1形成复合体。这两种细胞受体的交替使用可能对HTLV-1的神经趋向性有重要的意义。(C)2009 Elsevier Inc.保留所有权利。
Recent studies have demonstrated that neuropilin 1 (NP-1) is involved in HTLV-1 entry; however, the role NP-1 plays in this process is not understood. We demonstrated that ectopic expression of human NP-1 but not NP-2 cDNA increased susceptibility to HTLV-1. SiRNA-mediated inhibition of NP-1 expression correlated with significant reduction of HTLV-1 Env-mediated fusion. The vascular endothelial growth factor (VEGF(165)) caused downmodulation of surface NP-1 and inhibited HTLV-1 infection of U87 cells. In contrast, VEGF(165) partially inhibited infection of primary astrocytes and had no significant effect on infection of HeLa cells. VEGF(165) and antibodies to the glucose transporter protein 1 (anti-GLUT-1) were both needed to block infection of primary astrocytes, however, only anti-GLUT-1 antibodies were sufficient to block infection of HeLa cells. HTLV-1 Env forms complexes with both NP-1 and GLUT-1 in primary human astrocytes. The alternate usage of these two cellular receptors may have important implications regarding HTLV-1 neuro-tropism. (C) 2009 Elsevier Inc. All rights reserved.