HIV-1-Induced miR-146a Attenuates Monocyte Migration by Targeting CCL5 in Human Primary Macrophages
HIV-1-Induced miR-146a Attenuates Monocyte Migration by Targeting CCL5 in Human Primary Macrophages
复制标题
HIV-1 诱导的 miR-146a 通过靶向人原代巨噬细胞中的 CCL5 来减弱单核细胞迁移。
DOI：
10.1089/aid.2017.0217
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发表时间：
2018-05-30
影响因子：
1.5
通讯作者：
Feng, Yong
中科院分区：
文献类型：
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作者：
Huang, Qiuling;Chen, Lang;Feng, Yong
MicroRNAs （miRNAs）广泛参与病毒感染过程中的免疫调节。几项研究表明，miR-146a在人类免疫缺陷病毒I型（HIV-1）感染的细胞中表达增加，但miR-146a在HIV-1感染中的确切功能仍不清楚。据报道，巨噬细胞中趋化因子（C-C基序）配体5 （CCL5）的产生在HIV/ aids相关发病机制中起重要作用。在这项研究中，我们检测了miR-146a对hiv -1感染巨噬细胞中CCL5调控的影响。功能的获得和丧失研究表明，CCL5可能是miR-146a的靶点之一，因为miR-146a模拟物减少，而miR-146a抑制剂增加了hiv -1感染巨噬细胞中CCL5的产生。此外，我们证明了miR-146a减少了ccl5诱导的单核细胞迁移。我们的研究证明，miR-146a靶向ccl53非翻译区，下调其从巨噬细胞中的释放，从而影响单核细胞的迁移。这些发现揭示了miR-146a在HIV感染过程中对趋化因子CCL5的转录后调控的新层面，这可能有助于HIV的发病机制。
MicroRNAs (miRNAs) are widely involved in immune regulation during virus infection. Several studies showed that the expression of miR-146a was increased in human immunodeficiency virus type I (HIV-1)-infected cells, but the definitive function of miR-146a in HIV-1 infection remains obscure. The production of chemokine (C-C motif) ligand 5 (CCL5) in macrophages has been reported to play an important role in HIV/AIDS-associated pathogenesis. In this study, we examined the effects of miR-146a on CCL5 regulation in HIV-1-infected macrophages. Gain and loss of function studies showed that CCL5 might be one of the miR-146a targets, as miR-146a mimic reduced, while miR-146a inhibitor increased CCL5 production in HIV-1-infected macrophages. In addition, we demonstrated that miR-146a reduced CCL5-induced monocyte migration. Our study provided evidence that miR-146a targets CCL5 3 untranslated regions, downregulates its release from macrophages, and affects monocyte migration consequently. These findings drew a novel layer of posttranscriptional control of the chemokine CCL5 by miR-146a during HIV infection, which might contribute to HIV pathogenesis.