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HIV-1 matrix protein p17 binds to monocytes and selectively stimulates MCP-1 secretion: role of transcriptional factor AP-1.

Marini E, Tiberio L, Caracciolo S, Tosti G, Guzman CA, Schiaffonati L, Fiorentini S, Caruso A

Department of Applied and Experimental Medicine, Section of Microbiology, University of Brescia, Brescia, Italy.

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.

Published 8 February 2008 in Cell Microbiol, 10(3): 655-66.
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