title: Mumps virus inhibits migration of primary human macrophages toward a chemokine gradient through a TNF-alpha dependent mechanism.
abstract: Macrophages are an important cell type for regulation of immunity, and can play key roles in virus pathogenesis. Here we address the effect of infection of primary human macrophages with the related paramyxoviruses Parainfluenza virus 5 (PIV5) and Mumps virus (MuV). Monocyte-derived macrophages infected with PIV5 or MuV showed very little cytopathic effect, but were found to be defective in migration toward a gradient of chemokines such as macrophage colony stimulating factor (MCSF) and vascular endothelial growth factor (VEGF). For MuV infection, the inhibition of migration required live virus infection, but was not caused by a loss of chemokine receptors on the surface of infected cells. MuV-mediated inhibition of macrophage chemotaxis was through a soluble factor released from infected cells. MuV infection enhanced secretion of TNF-α, but not macrophage inhibitory factor (MIF). Antibody inhibition and add-back experiments demonstrated that TNF-α was both necessary and sufficient for MuV-mediate chemotaxis inhibition.
authors.affiliation: Department of Microbiology and Immunology, Wake Forest School of Medicine, Winston-Salem, NC 27157-1064, USA.
authors.forename: Caitlin M
authors.initials: CM
authors.lastname: Briggs
authors.forename: Anne E
authors.initials: AE
authors.lastname: Mayer
authors.forename: Griffith D
authors.initials: GD
authors.lastname: Parks
mesh_terms: D002464:Cell Migration Inhibition / Q000187:drug effects*; D002633:Chemotaxis / Q000187:drug effects; D054884:Host-Pathogen Interactions; D006801:Humans; D057131:Immune Evasion; D019746:Intramolecular Oxidoreductases / Q000378:metabolism; D016173:Macrophage Colony-Stimulating Factor / Q000276:immunology / Q000494:pharmacology; D008263:Macrophage Migration-Inhibitory Factors / Q000378:metabolism; D008264:Macrophages / Q000276:immunology / Q000821:virology*; D009109:Mumps virus / Q000502:physiology*; D061251:Primary Cell Culture; D019707:Receptors, Chemokine / Q000276:immunology; D018108:Respirovirus / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology*; D042461:Vascular Endothelial Growth Factor A / Q000276:immunology / Q000494:pharmacology
chemical_list: D008263:Macrophage Migration-Inhibitory Factors; D019707:Receptors, Chemokine; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; D016173:Macrophage Colony-Stimulating Factor; D019746:Intramolecular Oxidoreductases; C515598:MIF protein, human