Author: Marini, Elena; Tiberio, Laura; Caracciolo, Sonia; Tosti, Giorgio; Guzman, Carlos A.; Schiaffonati, Luisa; Fiorentini, Simona; Caruso, Arnaldo
Title: HIVâ€1 matrix protein p17 binds to monocytes and selectively stimulates MCPâ€1 secretion: role of transcriptional factor APâ€1 Cord-id: g5r2b043 Document date: 2007_10_26
ID: g5r2b043
Snippet: HIVâ€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 HIVâ€1 reservoir, is not known. Here we show that human monocytes constitutively express p17Rs and that p17 selectively triggers these cells to produce MCPâ€1. The effect of p17 on MCPâ€1 expression was o
Document: HIVâ€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 HIVâ€1 reservoir, is not known. Here we show that human monocytes constitutively express p17Rs and that p17 selectively triggers these cells to produce MCPâ€1. The effect of p17 on MCPâ€1 expression was observed at the transcriptional level and was primarily dependent on the activation of the transcription factor APâ€1. p17 increased the binding activity of APâ€1 complexes in a time†and doseâ€dependent manner. Deletion of the APâ€1 binding sites in the MCPâ€1 promoter resulted in the lack of p17â€induced MCPâ€1 transcription. In particular, the P3 binding site located between −69 and −63 position seems to be essential to MCPâ€1 mRNA induction in p17â€treated monocytes. An ever increasing amount of evidences shows a tight link between biologically dysregulated monocytes, APâ€1 activation, MCPâ€1 release and HIVâ€1 pathogenesis. Overall our results suggest that p17 may play a critical role in the monocyteâ€mediated inflammatory processes, which are suspected to be major precipitating events in AIDSâ€defining diseases.
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