Microglia express CCR5, CXCR4, and CCR3, but of these, CCR5 is the principal coreceptor for human immunodeficiency virus type 1 dementia isolates
Microglia express CCR5, CXCR4, and CCR3, but of these, CCR5 is the principal coreceptor for human immunodeficiency virus type 1 dementia isolates
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DOI：
10.1128/jvi.73.1.205-213.1999
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发表时间：
1999-01-01
影响因子：
5.4
通讯作者：
González-Scarano, F
中科院分区：
文献类型：
--
作者：
Albright, AV;Shieh, JTC;González-Scarano, F
小胶质细胞是中枢神经系统中主要的人类免疫缺陷病毒 (HIV) 储存库，很可能在艾滋病毒痴呆 (HIVD) 的发展中发挥重要作用。为了表征人类成人小胶质细胞趋化因子受体，我们分析了 CCR5、CCR3 和 CXCR4 的表达和钙信号传导及其在 HIV 进入中的作用。小胶质细胞表达的 CCR5 水平高于 CCR3 或 CXCR4。根据单细胞钙流实验记录，在这三种趋化因子受体中，只有 CCR5 和 CXCR4 能够在小胶质细胞中转导信号，以响应其各自的配体 MIP-1 beta 和 SDF-1 alpha。我们还发现，CCR5 是 HIV 1 型痴呆分离株 HIV-1(DS-br)、HIV-1(RC-br) 和 HIV-1(YU-2) 感染成人小胶质细胞的主要辅助受体，因为抗 CCR5 抗体 2D7 能够显着抑制野生型和单轮荧光素酶假型报告病毒对小胶质细胞的感染。抗 CCR3 (7B11) 和抗 CXCR4 (12G5) 抗体对感染影响很小或没有影响。最后，我们发现用 DS-br 和 RC-br 包膜假型化的病毒可以感染 CD4 与 G 蛋白偶联受体 APJ、CCR8 和 GPR15 一起转染的细胞，这些受体先前已被认为与 HIV 进入有关。
Microglia are the main human immunodeficiency virus (HIV) reservoir in the central nervous system and most likely play a major role in the development of HIV dementia (HIVD). To characterize human adult microglial chemokine receptors, we analyzed the expression and calcium signaling of CCR5, CCR3, and CXCR4 and their roles in HIV entry. Microglia expressed higher levels of CCR5 than of either CCR3 or CXCR4. Of these three chemokine receptors, only CCR5 and CXCR4 were able to transduce a signal in microglia in response to their respective ligands, MIP-1 beta and SDF-1 alpha, as recorded by single-cell calcium flux experiments. We also found that CCR5 is the predominant coreceptor used for infection of human adult microglia by the HIV type 1 dementia isolates HIV-1(DS-br), HIV-1(RC-br), and HIV-1(YU-2), since the anti-CCR5 antibody 2D7 was able to dramatically inhibit microglial infection by both wild-type and single-round luciferase pseudotype reporter viruses. Anti-CCR3 (7B11) and anti-CXCR4 (12G5) antibodies had little or no effect on infection. Last, we found that virus pseudotyped with the DS-br and RC-br envelopes can infect cells transfected with CD4 in conjunction with the G-protein-coupled receptors APJ, CCR8, and GPR15, which have been previously implicated in HIV entry.