Chemokine signaling and HIV‐1 fusion mediated by macrophage CXCR4: implications for target cell tropism
Chemokine signaling and HIV‐1 fusion mediated by macrophage CXCR4: implications for target cell tropism
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巨噬细胞 CXCR4 介导的趋化因子信号传导和 HIV-1 融合：对靶细胞趋向性的影响
DOI：
10.1189/jlb.68.3.318
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发表时间：
2000
影响因子：
5.5
通讯作者：
B. Freedman
中科院分区：
文献类型：
--
作者：
R. Collman;Y. Yi;Qing Liu;B. Freedman
为了更好地了解CXCR4在巨噬细胞上的功能，以及不同HIV - 1分离株中辅助受体使用与巨噬细胞嗜性之间的关系，我们分析了参与Env介导融合、产生性HIV - 1感染和趋化因子诱导信号传导的巨噬细胞途径。我们发现CXCR4和CCR5分别在单核细胞来源的巨噬细胞中转导细胞内信号，激活K+和Cl -离子通道，并在它们的趋化因子配体基质细胞来源因子- 1α和巨噬细胞炎症蛋白- 1β的作用下升高细胞内钙。原型嗜T型X4菌株IIIB对巨噬细胞的感染较差，这与尽管CXCR4功能良好，但IIIB Env无法与目标巨噬细胞有效融合有关。相反，一些原代X4分离物介导了高效的CXCR4依赖性融合和巨噬细胞感染。一些R5X4菌株可以通过CCR5和CXCR4与巨噬细胞融合并感染巨噬细胞。因此，巨噬细胞表达功能性的CXCR4和CCR5，但原代和原型分离的X4在利用巨噬细胞CXCR4的能力上存在差异。根据辅助受体的使用被分类为X4的分离株在表型上可能是T向或双向的，相反，根据辅助受体的使用，表型上双向的分离株可能是R5X4或X4。
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‐1α and macrophage inflammatory protein‐1β, 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.
使用表达不同 RNA 聚合酶的双重组牛痘病毒快速筛选克隆的 HIV-1 Env 的巨噬细胞融合测定。
影响因子：
3.1
作者：
Isaacs,SN;Yi,Y;Singh,A;Collman,RG
通讯作者：
Collman,RG
影响因子：
3.7
作者：
Dimitrov, DS;Norwood, D;Broder, CC
通讯作者：
Broder, CC
DOI：
10.1073/pnas.96.9.5215
发表时间：
1999-04-27
影响因子：
11.1
作者：
Lee, B;Sharron, M;Doms, RW
通讯作者：
Doms, RW