title: Ebola and Marburg viruses replicate in monocyte-derived dendritic cells without inducing the production of cytokines and full maturation.
abstract: Ebola virus (EBOV) and Marburg virus (MARV) cause rapidly progressive hemorrhagic fever with high mortality and may possess specialized mechanisms to evade immune destruction. We postulated that immune evasion could be due to the ability of EBOV and MARV to interfere with dendritic cells (DCs), which link innate and adaptive immune responses. We demonstrate that EBOV and MARV infected and replicated in primary human DCs without inducing cytokine secretion. Infected DC cultures supported exponential viral growth without releasing interferon (IFN)-alpha and were impaired in IFN-alpha production if treated with double-stranded RNA. Moreover, EBOV and MARV impaired the ability of DCs to support T cell proliferation, and infected, immature DCs underwent an anomalous maturation. These findings may explain the profound virulence of EBOV and MARV--DCs are disabled, and an effective early host response is delayed by the necessary reliance on less-efficient secondary mechanisms.
authors.affiliation: United States Army Medical Research Institute of Infectious Diseases, Frederick, Maryland 21702-5011, USA.
authors.forename: Catharine M
authors.initials: CM
authors.lastname: Bosio
authors.forename: M Javad
authors.initials: MJ
authors.lastname: Aman
authors.forename: Case
authors.initials: C
authors.lastname: Grogan
authors.forename: Robert
authors.initials: R
authors.lastname: Hogan
authors.forename: Gordon
authors.initials: G
authors.lastname: Ruthel
authors.forename: Diane
authors.initials: D
authors.lastname: Negley
authors.forename: Mansour
authors.initials: M
authors.lastname: Mohamadzadeh
authors.forename: Sina
authors.initials: S
authors.lastname: Bavari
authors.forename: Alan
authors.initials: A
authors.lastname: Schmaljohn
mesh_terms: D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis*; D003713:Dendritic Cells / Q000276:immunology / Q000821:virology*; D029043:Ebolavirus / Q000472:pathogenicity*; D006801:Humans; D029024:Marburgvirus / Q000472:pathogenicity*; D013601:T-Lymphocytes / Q000276:immunology; D014779:Virus Replication
chemical_list: D016207:Cytokines