HIV-1 matrix protein p17 binds to monocytes and selectively stimulates MCP-1 secretion: role of transcriptional factor AP-1
HIV-1 matrix protein p17 binds to monocytes and selectively stimulates MCP-1 secretion: role of transcriptional factor AP-1
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DOI：
10.1111/j.1462-5822.2007.01073.x
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发表时间：
2008-03-01
影响因子：
3.4
通讯作者：
Caruso, Arnaldo
中科院分区：
文献类型：
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作者：
Marini, Elena;Tiberio, Laura;Caruso, Arnaldo
HIV-1 基质蛋白 p17 激活多种细胞反应，在病毒复制和感染中发挥关键作用。其活性取决于靶细胞表面p17受体（p17R）的表达。 p17 是否也在刺激人类单核细胞（HIV-1 的主要储存库）中发挥作用尚不清楚。在这里，我们证明人类单核细胞组成型表达 p17R，并且 p17 选择性触发这些细胞产生 MCP-1。 p17 对 MCP-1 表达的影响是在转录水平上观察到的，并且主要取决于转录因子 AP-1 的激活。 p17 以时间和剂量依赖性方式增加 AP-1 复合物的结合活性。 MCP-1 启动子中 AP-1 结合位点的缺失导致 p17 诱导的 MCP-1 转录缺失。特别是，位于 -69 和 -63 位置之间的 P3 结合位点似乎对于 p17 处理的单核细胞中 MCP-1 mRNA 的诱导至关重要。越来越多的证据表明，单核细胞生物学失调、AP-1 激活、MCP-1 释放和 HIV-1 发病机制之间存在密切联系。总的来说，我们的结果表明 p17 可能在单核细胞介导的炎症过程中发挥关键作用，单核细胞介导的炎症过程被怀疑是艾滋病定义疾病的主要诱发事件。
HIV-1 matrix protein p17 activates a variety of cell responses which play a critical role in viral replication and infection. Its activity depends on the expression of p17 receptors (p17R) on the surface of target cells. Whether p17 also plays a role in stimulating human monocytes, a major HIV-1 reservoir, is not known. Here we show that human monocytes constitutively express p17Rs and that p17 selectively triggers these cells to produce MCP-1. The effect of p17 on MCP-1 expression was observed at the transcriptional level and was primarily dependent on the activation of the transcription factor AP-1. p17 increased the binding activity of AP-1 complexes in a time- and dose-dependent manner. Deletion of the AP-1 binding sites in the MCP-1 promoter resulted in the lack of p17-induced MCP-1 transcription. In particular, the P3 binding site located between -69 and -63 position seems to be essential to MCP-1 mRNA induction in p17-treated monocytes. An ever increasing amount of evidences shows a tight link between biologically dysregulated monocytes, AP-1 activation, MCP-1 release and HIV-1 pathogenesis. Overall our results suggest that p17 may play a critical role in the monocyte-mediated inflammatory processes, which are suspected to be major precipitating events in AIDS-defining diseases.