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Updated: Sep 28, 2026
Isolation, Transfection, and Culture of Primary Human Monocytes
Published on: December 16, 2019
Human cytomegalovirus infection reduces surface CCR5 expression in human microglial cells, astrocytes and
Didier Lecointe1, Nathalie Dugas, Philippe Leclerc
1Laboratoire 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
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.
Insights
Human cytomegalovirus (HCMV) infection reduces cell-surface expression of HIV co-receptors on brain cells. This suggests HCMV may impair HIV-1 entry into microglia and macrophages.
Area of Science:
- Neurovirology
- Immunology
- Cell Biology
Background:
- Glial cells, including microglia and astrocytes, are targets for human cytomegalovirus (HCMV) and human immunodeficiency virus (HIV).
- CCR5 and CXCR4 are critical co-receptors for HIV-1 entry into host cells.
Purpose of the Study:
- To investigate the effect of HCMV infection on the expression of HIV co-receptors (CCR5, CXCR4, CD4) in human glial cells and monocyte-derived macrophages (MDM).
- To determine the impact of HCMV-HIV co-infection on HIV replication in these cells.
Main Methods:
- Primary human microglial cells, astrocytes, and MDM were infected with HCMV strain AD169.
- Cells were subsequently co-infected with HIV-1 monocytotropic strains, either simultaneously or sequentially.
- Expression of co-receptors and viral proteins was assessed using immunofluorescence and p24 antigen levels were measured in cell supernatants.
Main Results:
- HCMV infection led to down-regulation of CCR5 on microglia, astrocytes, and MDM.
- HCMV infection reduced CXCR4 and CD4 expression specifically on microglial cells.
- Co-infection resulted in cytoplasmic co-localization of HCMV and HIV-1 proteins.
- p24 antigen levels significantly decreased in MDM supernatants, with a more pronounced reduction when HCMV preceded HIV-1 infection.
Conclusions:
- HCMV infection alters the expression of essential HIV-1 co-receptors on glial cells and MDM.
- HCMV-induced down-regulation of CCR5 may represent a mechanism by which HCMV interferes with HIV-1 infection of these critical brain cells.
