Role of interferon alpha (IFN-alpha) and interferon gamma (IFN-gamma) in the control of the infection of monocyte-like cells with human cytomegalovirus (HCMV).
The role of cytokines in the control of HCMV infection has been studied in THP-1 cells, a macrophage-like cell model and in MRC-5 cells. HCMV replication was studied by immune detection of viral immediate-early antigens (IEA) and virus yield was evaluated in MRC-5 cells by immunoperoxidase staining. Pretreatment of MRC-5 and phorbol 12-myristate 13-acetate (PMA)-treated THP-1 cells with IFN-alpha or IFN-gamma for 24 hr prior to the infection reduced the number of infected cells and virus yield. A synergistic anti-CMV activity in synthesis of early proteins was obtained with these cytokines in combination with TNF-alpha in differentiated THP-1 cells only. Treatment of HCMV-infected differentiated THP-1 cells or MRC-5 cells with IFN-alpha or IFN-gamma alone had no inhibitory effect on virus replication, however the virus yield was reduced with ganciclovir. A synergistic anti-CMV activity in virus yield was obtained only when infected differentiated THP-1 cells were treated with ganciclovir in combination with IFN-gamma. The current study shows that IFN-alpha and IFN-gamma can play a role in the reduction of HCMV replication in macrophage-like cells and in the efficiency of therapies with ganciclovir in this cell type and that the anti-CMV effect of cytokines may be different in fibroblasts and in macrophage-like cells.
Delannoy
A S
AS
Laboratoire de Virologie, Institut Gernez Rieux, Centre Hospitalier et Universitaire de Lille, France.
Hober
D
D
Bouzidi
A
A
Wattre
P
P
D000998:Antiviral Agents / Q000494:pharmacology; D002460:Cell Line; D003587:Cytomegalovirus / Q000276:immunology* / Q000502:physiology; D003586:Cytomegalovirus Infections / Q000276:immunology / Q000517:prevention & control*; D005347:Fibroblasts / Q000187:drug effects / Q000276:immunology / Q000821:virology; D015774:Ganciclovir / Q000494:pharmacology; D006801:Humans; D016898:Interferon-alpha / Q000276:immunology* / Q000494:pharmacology; D007371:Interferon-gamma / Q000276:immunology* / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000821:virology; D011994:Recombinant Proteins / Q000276:immunology / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology* / Q000494:pharmacology
D000998:Antiviral Agents; D016898:Interferon-alpha; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D015774:Ganciclovir