Human cytomegalovirus infection reduces surface CCR5 expression in human microglial cells, astrocytes and monocyte-derived macrophages.
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.
Lecointe
Didier
D
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
Dugas
Nathalie
N
Leclerc
Philippe
P
Hery
Christiane
C
Delfraissy
Jean-François
JF
Tardieu
Marc
M
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
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