title: Human cytomegalovirus infection reduces surface CCR5 expression in human microglial cells, astrocytes and monocyte-derived macrophages.
abstract: Within the brain, glial cells are target cells for human cytomegalovirus (HCMV) and HIV. We infected cultures of unstimulated human microglial cells and astrocytes of embryonic origin and of monocyte-derived macrophages (MDM) with HCMV strain AD169 and observed down-regulation of the plasma membrane expression of CCR5 in the three cell types, and of CXCR4 and CD4 in microglial cells only. Cells were then coinfected simultaneously or at a 24-h interval with both AD169 and two different HIV-1 monocytotropic strains. HCMV late antigens and HIV-1 tat protein colocalized in the cytoplasm of 5-10% of microglia and MDM. p24 antigen levels decreased 10- to 40-fold in supernatants of MDM and the reduction was greater when HCMV infection was performed 24 h before HIV-1 infection. These data suggest that HCMV-induced reduction in the cell-surface expression of the primary co-receptor of HIV-1 monocytotropic strains may impair the ability of HIV to infect these cells.
authors.affiliation: Laboratoire Inserm E-0109, Immunité antivirale systémique et cérébrale, 63, rue Gabriel Péri, Faculté de Médecine Paris-Sud, 94276 Le Kremlin Bicêtre cedex, France. didier.lecointe@ch-sud-francilien.fr
authors.forename: Didier
authors.initials: D
authors.lastname: Lecointe
authors.forename: Nathalie
authors.initials: N
authors.lastname: Dugas
authors.forename: Philippe
authors.initials: P
authors.lastname: Leclerc
authors.forename: Christiane
authors.initials: C
authors.lastname: Hery
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Delfraissy
authors.forename: Marc
authors.initials: M
authors.lastname: Tardieu
mesh_terms: D000956:Antigens, Viral / Q000032:analysis; D001253:Astrocytes / Q000378:metabolism / Q000821:virology*; D015704:CD4 Antigens / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D054407:Chemokine CCL4; D018946:Chemokine CCL5 / Q000032:analysis; D003587:Cytomegalovirus / Q000254:growth & development / Q000502:physiology*; D003586:Cytomegalovirus Infections / Q000378:metabolism; D016655:HIV Core Protein p24 / Q000032:analysis; D015497:HIV-1 / Q000254:growth & development / Q000378:metabolism; D006801:Humans; D019402:Macrophage Inflammatory Proteins / Q000032:analysis; D008264:Macrophages / Q000378:metabolism / Q000821:virology*; D017628:Microglia / Q000378:metabolism / Q000821:virology*; D009000:Monocytes / Q000166:cytology / Q000502:physiology; D019713:Receptors, CCR5 / Q000276:immunology / Q000378:metabolism*; D019718:Receptors, CXCR4 / Q000276:immunology / Q000378:metabolism; D019707:Receptors, Chemokine / Q000235:genetics / Q000378:metabolism; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism; D014779:Virus Replication
chemical_list: D000956:Antigens, Viral; D015704:CD4 Antigens; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D016655:HIV Core Protein p24; D019402:Macrophage Inflammatory Proteins; D019713:Receptors, CCR5; D019718:Receptors, CXCR4; D019707:Receptors, Chemokine; C411191:US28 receptor, Cytomegalovirus; D014764:Viral Proteins