Bleul C C, Farzan M, Choe H, Parolin C, Clark-Lewis I, Sodroski J, Springer T A
The Center for Blood Research, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA.
Nature. 1996 Aug 29;382(6594):829-33. doi: 10.1038/382829a0.
Chemokines are chemotactic cytokines that activate and direct the migration of leukocytes. There are two subfamilies, the CXC and the CC chemokines. We recently found that the CXC-chemokine stromal cell-derived factor-1 (SDF-1) is a highly efficacious lymphocyte chemoattractant. Chemokines act on responsive leukocyte subsets through G-protein-coupled seven-transmembrane receptors, which are also used by distinct strains of HIV-1 as cofactors for viral entry. Laboratory-adapted and some T-cell-line-tropic (T-tropic) primary viruses use the orphan chemokine receptor LESTR/fusin (also known as fusin), whereas macrophage-tropic primary HIV-1 isolates use CCR-5 and CCR-3 (refs 7-11), which are receptors for known CC chemokines. Testing of potential receptors demonstrated that SDF-1 signalled through, and hence 'adopted', the orphan receptor LESTR, which we therefore designate CXC-chemokine receptor-4 (CXCR-4). SDF-1 induced an increase in intracellular free Ca2+ and chemotaxis in CXCR-4-transfected cells. Because SDF-1 is a biological ligand for the HIV-1 entry cofactor LESTR, we tested whether it inhibited HIV-1. SDF-1 inhibited infection by T-tropic HIV-1 of HeLa-CD4 cells, CXCR-4 transfectants, and peripheral blood mononuclear cells (PBMCs), but did not affect CCR-5-mediated infection by macrophage-tropic (M-tropic) and dual-tropic primary HIV-1.
趋化因子是一类趋化性细胞因子，可激活并指导白细胞的迁移。趋化因子有两个亚家族，即CXC趋化因子和CC趋化因子。我们最近发现，CXC趋化因子基质细胞衍生因子-1（SDF-1）是一种高效的淋巴细胞趋化剂。趋化因子通过G蛋白偶联的七跨膜受体作用于有反应的白细胞亚群，不同株的HIV-1也将这些受体用作病毒进入的辅助因子。实验室适应株和一些T细胞系嗜性（T嗜性）原代病毒使用孤儿趋化因子受体LESTR/fusin（也称为fusin），而巨噬细胞嗜性原代HIV-1分离株使用CCR-5和CCR-3（参考文献7-11），它们是已知CC趋化因子的受体。对潜在受体的检测表明，SDF-1通过孤儿受体LESTR发出信号，因此“采用”了该受体，我们因此将其命名为CXC趋化因子受体-4（CXCR-4）。SDF-1在转染了CXCR-4的细胞中诱导细胞内游离Ca2+增加和趋化作用。由于SDF-1是HIV-1进入辅助因子LESTR的生物配体，我们测试了它是否能抑制HIV-1。SDF-1抑制HeLa-CD4细胞、CXCR-4转染细胞和外周血单核细胞（PBMC）受T嗜性HIV-1的感染，但不影响巨噬细胞嗜性（M嗜性）和双嗜性原代HIV-1介导的CCR-5感染。
