title: Monocyte-derived human macrophages and peripheral blood mononuclear cells infected with ebola virus secrete MIP-1alpha and TNF-alpha and inhibit poly-IC-induced IFN-alpha in vitro.
abstract: Ebola virus infection of humans is associated with high levels of circulating inflammatory chemokines and cytokines. We demonstrate that direct infection of human PBMC results in the induction of MCP-1, MIP-1alpha, RANTES, and TNF-alpha as early as 24 h p.i. in response to live virus. Monocyte-derived macrophages infected with live Ebola-virus secreted MIP-1alpha and TNF-alpha specifically while RANTES and MCP-1 were secreted by with both live or inactivated virus stimulation and do not require viral replication. Type I interferons (IFN-alpha and -beta), IL-1beta and IL-10, were not induced by Ebola virus. Furthermore, live virus infection of both PBMCs and monocytes-derived macrophages inhibited IFN-alpha induced by double-stranded RNA in vitro. These data provide the first direct evidence of a role for macrophages in the pathogenesis to Ebola virus and suggest that Ebola virus can inhibit cellular antiviral mechanisms mediated by type I interferons.
authors.affiliation: Emory Vaccine Center, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
authors.forename: M
authors.initials: M
authors.lastname: Gupta
authors.forename: S
authors.initials: S
authors.lastname: Mahanty
authors.forename: R
authors.initials: R
authors.lastname: Ahmed
authors.forename: P E
authors.initials: PE
authors.lastname: Rollin
mesh_terms: D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000097:blood; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5 / Q000097:blood; D029043:Ebolavirus; D004797:Enzyme-Linked Immunosorbent Assay; D019142:Hemorrhagic Fever, Ebola / Q000097:blood*; D006801:Humans; D016898:Interferon-alpha / Q000097:blood*; D016899:Interferon-beta / Q000097:blood; D007375:Interleukin-1 / Q000097:blood; D016753:Interleukin-10 / Q000097:blood; D019402:Macrophage Inflammatory Proteins / Q000097:blood*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism / Q000821:virology*; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism / Q000821:virology*; D011070:Poly I-C / Q000494:pharmacology*; D012330:RNA, Double-Stranded / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D018932:Chemokine CCL2; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D016898:Interferon-alpha; D007375:Interleukin-1; D019402:Macrophage Inflammatory Proteins; D012330:RNA, Double-Stranded; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D016899:Interferon-beta; D011070:Poly I-C