title: SDF-1-induced activation of ERK enhances HIV-1 expression.
abstract: Chemokine receptors are not only able to bind chemokines but, together with CD4, they serve as an entry door for the human immunodeficiency virus type 1 (HIV-1). The signalling capacity of chemokine receptors, which is of fundamental importance for chemokine-induced chemotaxis, is not used by HIV-1 to enter a target cell, nor by chemokines or chemokine-derived ligands to inhibit viral entry. In addition, an ill-defined signal triggered by chemokines can, under some circumstances, lead to an increase in HIV-1 expression. We show here that, in infected cells, exposure to SDF-1 leads to an increased expression of a X4 strain of HIV-1. A similar increase can be induced by an N-terminal peptide of SDF-1 which had previously been shown to elicit an intracellular calcium response and to inhibit the entry of X4 strains of HIV-1. We demonstrate the involvement of extracellular signal-regulated kinases (ERK) in this phenomenon. SDF-1 activates ERK-1 and ERK-2 in Jurkat cells. In HeLa cells, ERK-2 only is activated by SDF-1 or by a SDF-derived peptide. This ERK activation can be blocked by pertussis toxin and by the MEK inhibitor U0126. Most importantly, SDF-1-dependent HIV-1 expression is abolished by pretreating the cells with pertussis toxin or with U0126. The consequences of this SDF-1-induced, ERK-dependent modulation of HIV-1 expression in infected cells may have a clinical relevance for eradicating latent viruses.
authors.affiliation: CNRS UMR 7627, CERVI, CHU Pitié-Salpêtrière, 75013 Paris, France.
authors.forename: M
authors.initials: M
authors.lastname: Montes
authors.forename: N E
authors.initials: NE
authors.lastname: Tagieva
authors.forename: N
authors.initials: N
authors.lastname: Heveker
authors.forename: C
authors.initials: C
authors.lastname: Nahmias
authors.forename: F
authors.initials: F
authors.lastname: Baleux
authors.forename: A
authors.initials: A
authors.lastname: Trautmann
mesh_terms: D019380:Anti-HIV Agents / Q000494:pharmacology*; D002070:Butadienes / Q000494:pharmacology; D015704:CD4 Antigens / Q000235:genetics / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D002453:Cell Cycle; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000494:pharmacology*; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016325:HIV Long Terminal Repeat / Q000235:genetics; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D019169:Jurkat Cells; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009570:Nitriles / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D019718:Receptors, CXCR4 / Q000502:physiology; D014158:Transcription, Genetic; D014162:Transfection; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D019380:Anti-HIV Agents; D002070:Butadienes; D015704:CD4 Antigens; C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D004791:Enzyme Inhibitors; D009570:Nitriles; D010446:Peptide Fragments; D019718:Receptors, CXCR4; C113580:U 0126; D020928:Mitogen-Activated Protein Kinases; D002118:Calcium