Inhibition of CMV replication in human fibroblasts by human monocyte-derived macrophages: implication for CMV persistent infection.
The effect of monocytes (M) and monocyte-derived macrophages (MdM) on cytomegalovirus (CMV) replication in human fibroblasts (HF) was studied by one step growth experiments, plaque formation and dot hybridization with a labeled CMV DNA probe. HF were infected with CMV at multiplicities of infection (mol) of 0.001 to 1. After virus adsorption, M or MdM were added at an effector target ratio of 2:1. MdM reduced both infectious viral yield and the quantity of viral DNA and inhibited viral plaque formation. M, however, affected these parameters to a lesser extent. Electron microscopic studies showed that MdM treated CMF-infected HF, 4 days pi, contained only a few capsids in their nuclei and many vacuoles in their cytoplasm as compared to CMV infected HF (control). A reduction of CMV DNA inhibition was observed upon incubation of the infected HF cells with MdM separated from the infected cells by a membrane. Addition of tumor necrosis factor (TNF) antibody to CMV-infected HF incubated with MdM either in direct contact or separated by a membrane from the infected cells reduced the inhibition of CMV-DNA production. The results of this study suggest that MdM may modulate CMV replication in vivo and may also have a role in CMV persistence or chronic infection.
Manor
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E
Virology Unit, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel.
Sarov
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I
D003587:Cytomegalovirus / Q000276:immunology / Q000502:physiology*; D003586:Cytomegalovirus Infections / Q000276:immunology; D004279:DNA, Viral / Q000032:analysis; D005347:Fibroblasts / Q000382:microbiology; D006801:Humans; D008264:Macrophages / Q000276:immunology*; D009000:Monocytes / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology; D014779:Virus Replication
D004279:DNA, Viral; D014409:Tumor Necrosis Factor-alpha