HIV-1 matrix protein p17 binds to monocytes and selectively stimulates MCP-1 secretion: role of transcriptional factor AP-1
| Autor: | Laura Tiberio, Arnaldo Caruso, Sonia Caracciolo, Simona Fiorentini, Giorgio Tosti, Elena Marini, Carlos A. Guzmán, Luisa Schiaffonati |
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| Rok vydání: | 2008 |
| Předmět: |
Transcription
Genetic HIV Antigens viruses Immunology Biology gag Gene Products Human Immunodeficiency Virus Microbiology Monocytes Downregulation and upregulation immune system diseases Transcription (biology) Virology Humans Secretion Binding site Promoter Regions Genetic Receptor Transcription factor Cells Cultured Chemokine CCL2 Sequence Deletion Messenger RNA Binding Sites Viral matrix protein virus diseases Original Articles Molecular biology Up-Regulation Transcription Factor AP-1 HIV-1 |
| Zdroj: | Cellular Microbiology |
| ISSN: | 1462-5822 1462-5814 |
| DOI: | 10.1111/j.1462-5822.2007.01073.x |
| Popis: | Summary 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. |
| Databáze: | OpenAIRE |
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