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首页> 外文期刊>Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society >Chemokine signaling and HIV-1 fusion mediated by macrophage CXCR4: implications for target cell tropism.
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Chemokine signaling and HIV-1 fusion mediated by macrophage CXCR4: implications for target cell tropism.

机译:巨噬细胞CXCR4介导的趋化因子信号传导和HIV-1融合:对靶细胞向性的影响。

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摘要

To better understand CXCR4 function on macrophages and the relationship between coreceptor use and macrophage tropism among diverse HIV-1 isolates, we analyzed macrophage pathways involved in Env-mediated fusion, productive HIV-1 infection, and chemokine-elicited signaling. We found that both CXCR4 and CCR5 transduced intracellular signals in monocyte-derived macrophages, activating K+ and Cl- ion channels and elevating intracellular calcium in response to their chemokine ligands stromal cell-derived factor-1alpha and macrophage inflammatory protein-1beta, respectively. The prototype T-tropic X4 strain IIIB infected macrophages poorly, and this was associated with failure of the IIIB Env to fuse efficiently with target macrophages despite functional CXCR4. In contrast, several primary X4 isolates mediated efficient CXCR4-dependent fusion and productive macrophage infection. Several R5X4 strains could fuse with and infect macrophages through both CCR5 and CXCR4. Thus, macrophages express functional CXCR4 and CCR5 but primary and prototype X4 isolates differ in their ability to utilize macrophage CXCR4. Isolates classified as X4 based on coreceptor use may be phenotypically either T-tropic or dual-tropic and, conversely, phenotypically dual-tropic isolates may be either R5X4 or X4 based on coreceptor use.
机译:为了更好地了解CXCR4在巨噬细胞上的功能以及各种HIV-1分离株之间共受体使用和巨噬细胞嗜性之间的关系,我们分析了Env介导的融合,生产性HIV-1感染和趋化因子诱发的信号传导中涉及的巨噬细胞途径。我们发现,CXCR4和CCR5分别在单核细胞衍生的巨噬细胞中转导细胞内信号,激活K +和Cl-离子通道,并响应其趋化因子配体基质细胞衍生因子1α和巨噬细胞炎性蛋白1beta升高细胞内钙。原型T-tropic X4菌株IIIB对巨噬细胞的感染较弱,这与IIIB Env无法有效融合目标巨噬细胞(尽管具有CXCR4功能)有关。相反,几个主要的X4分离株介导了有效的CXCR4依赖性融合和生产性巨噬细胞感染。几种R5X4菌株可以与CCR5和CXCR4融合并感染巨噬细胞。因此,巨噬细胞表达功能性CXCR4和CCR5,但是主要和原型X4分离株利用巨噬细胞CXCR4的能力不同。基于共受体的用途,分类为X4的分离株在表型上可以是T-向性或双向性的,相反,基于共受体的用途,在表型上双向分离株可以是R5X4或X4。

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