title: Differential activation profiles of Crimean-Congo hemorrhagic fever virus- and Dugbe virus-infected antigen-presenting cells.
abstract: Crimean-Congo hemorrhagic fever virus (CCHFV) is a highly pathogenic, tick-borne member of the family Bunyaviridae and the genus Nairovirus. To better elucidate the pathogenesis of CCHFV, we analysed the host innate immune response induced in antigen-presenting cells (APCs) infected in vitro by CCHFV. Monocyte-derived dendritic cells (DCs) and macrophages (MPs) were both shown to be permissive for CCHFV and to replicate the virus, as monitored by genomic and antigenomic strand quantification. Virus replication was, however, controlled, corroborating an efficient alpha interferon-induced response. The upregulation of CD-83 and CD-86 indicated that CCHFV induced a partial maturation of DCs, which were also shown to activate the secretion of interleukin (IL)-6 and IL-8, but no tumour necrosis factor alpha (TNF-alpha). On the other hand, in MPs, CCHFV infection elicited a high IL-6 and TNF-alpha response and a moderate chemokine response. Nevertheless, when we compared these APC responses with those seen after infection with Dugbe virus (DUGV), a mildly pathogenic virus genetically close to CCHFV, we found that, in spite of some similarities, DUGV induced a higher cytokine/chemokine response in MPs. These results suggest that CCHFV is able to inhibit the activation of inflammatory mediators selectively in infection in vitro and that these differences could be relevant in pathogenesis.
authors.affiliation: Emerging Pathogens Laboratory, Fondation Mérieux, IFR128 BioSciences Lyon-Gerland, Lyon, France.
authors.forename: Christophe N
authors.initials: CN
authors.lastname: Peyrefitte
authors.forename: Magali
authors.initials: M
authors.lastname: Perret
authors.forename: Stephan
authors.initials: S
authors.lastname: Garcia
authors.forename: Raquel
authors.initials: R
authors.lastname: Rodrigues
authors.forename: Audrey
authors.initials: A
authors.lastname: Bagnaud
authors.forename: Sandra
authors.initials: S
authors.lastname: Lacote
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Crance
authors.forename: Guy
authors.initials: G
authors.lastname: Vernet
authors.forename: Daniel
authors.initials: D
authors.lastname: Garin
authors.forename: Michèle
authors.initials: M
authors.lastname: Bouloy
authors.forename: Gláucia
authors.initials: G
authors.lastname: Paranhos-Baccalà
mesh_terms: D000938:Antigen-Presenting Cells / Q000276:immunology* / Q000821:virology*; D015703:Antigens, CD / Q000096:biosynthesis; D051940:B7-2 Antigen / Q000096:biosynthesis; D002478:Cells, Cultured; D018925:Chemokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology / Q000821:virology; D005786:Gene Expression Regulation; D003225:Hemorrhagic Fever Virus, Crimean-Congo / Q000276:immunology* / Q000472:pathogenicity*; D006801:Humans; D007136:Immunoglobulins / Q000096:biosynthesis; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D008264:Macrophages / Q000276:immunology / Q000821:virology; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D016855:Nairovirus / Q000276:immunology* / Q000472:pathogenicity*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015854:Up-Regulation; D014779:Virus Replication; D000097802:CD83 Antigen
chemical_list: D015703:Antigens, CD; D051940:B7-2 Antigen; D018925:Chemokines; D007136:Immunoglobulins; D015850:Interleukin-6; D016209:Interleukin-8; D008562:Membrane Glycoproteins; D014409:Tumor Necrosis Factor-alpha; D000097802:CD83 Antigen; C497964:CD86 protein, human