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 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.
Department of Applied and Experimental Medicine, Section of Microbiology, University of Brescia, Brescia, Italy.
Elena
E
Marini
Laura
L
Tiberio
Sonia
S
Caracciolo
Giorgio
G
Tosti
Carlos A
CA
Guzman
Luisa
L
Schiaffonati
Simona
S
Fiorentini
Arnaldo
A
Caruso
D001665:Binding Sites / Q000235:genetics; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism*; D015488:HIV Antigens / Q000378:metabolism*; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D009000:Monocytes / Q000821:virology*; D011401:Promoter Regions, Genetic; D017384:Sequence Deletion; D018808:Transcription Factor AP-1 / Q000502:physiology*; D014158:Transcription, Genetic / Q000235:genetics; D015854:Up-Regulation; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000378:metabolism*
C111835:CCL2 protein, human; D018932:Chemokine CCL2; D015488:HIV Antigens; D018808:Transcription Factor AP-1; D054301:gag Gene Products, Human Immunodeficiency Virus; C054858:p17 protein, Human Immunodeficiency Virus Type 1