title: Ebola virus infection kinetics in chimeric mice reveal a key role of T cells as barriers for virus dissemination.
abstract: Ebola virus (EBOV) causes severe systemic disease in humans and non-human primates characterized by high levels of viremia and virus titers in peripheral organs. The natural portals of virus entry are the mucosal surfaces and the skin where macrophages and dendritic cells (DCs) are primary EBOV targets. Due to the migratory properties of DCs, EBOV infection of these cells has been proposed as a necessary step for virus dissemination via draining lymph nodes and blood. Here we utilize chimeric mice with competent hematopoietic-driven immunity, to show that EBOV primarily infects CD11b+DCs in non-lymphoid and lymphoid tissues, but spares the main cross-presenting CD103+DC subset. Furthermore, depletion of CD8 and CD4 T cells resulted in loss of early control of virus replication, viremia and fatal Ebola virus disease (EVD). Thus, our findings point out at T cell function as a key determinant of EVD progress and outcome.
authors.affiliation: Heinrich Pette Institute, Leibniz Institute For Experimental Virology, Martinistrasse 52 20251 Hamburg, Germany.|Department of Virology, Bernhard Nocht Institute for Tropical Medicine, 20359 Hamburg, Germany.|German Center for Infection Research (DZIF), Partner site Hamburg, Germany.
authors.forename: Anja
authors.initials: A
authors.lastname: Lüdtke
authors.affiliation: Heinrich Pette Institute, Leibniz Institute For Experimental Virology, Martinistrasse 52 20251 Hamburg, Germany.|Department of Virology, Bernhard Nocht Institute for Tropical Medicine, 20359 Hamburg, Germany.|German Center for Infection Research (DZIF), Partner site Hamburg, Germany.
authors.forename: Paula
authors.initials: P
authors.lastname: Ruibal
authors.affiliation: Department of Virology, Bernhard Nocht Institute for Tropical Medicine, 20359 Hamburg, Germany.|German Center for Infection Research (DZIF), Partner site Hamburg, Germany.
authors.forename: David M
authors.initials: DM
authors.lastname: Wozniak
authors.affiliation: Department of Virology, Bernhard Nocht Institute for Tropical Medicine, 20359 Hamburg, Germany.|German Center for Infection Research (DZIF), Partner site Hamburg, Germany.
authors.forename: Elisa
authors.initials: E
authors.lastname: Pallasch
authors.affiliation: Department of Virology, Bernhard Nocht Institute for Tropical Medicine, 20359 Hamburg, Germany.|German Center for Infection Research (DZIF), Partner site Hamburg, Germany.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Wurr
authors.affiliation: Department of Virology, Bernhard Nocht Institute for Tropical Medicine, 20359 Hamburg, Germany.|German Center for Infection Research (DZIF), Partner site Hamburg, Germany.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Bockholt
authors.affiliation: Heinrich Pette Institute, Leibniz Institute For Experimental Virology, Martinistrasse 52 20251 Hamburg, Germany.
authors.forename: Sergio
authors.initials: S
authors.lastname: Gómez-Medina
authors.affiliation: Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, MB R3E 3R2, Canada.
authors.forename: Xiangguo
authors.initials: X
authors.lastname: Qiu
authors.affiliation: Department of Microbiology, Immunology &Infectious Diseases, Université Laval, Quebec City, Canada.
authors.forename: Gary P
authors.initials: GP
authors.lastname: Kobinger
authors.affiliation: Heinrich Pette Institute, Leibniz Institute For Experimental Virology, Martinistrasse 52 20251 Hamburg, Germany.
authors.forename: Estefanía
authors.initials: E
authors.lastname: Rodríguez
authors.affiliation: Department of Virology, Bernhard Nocht Institute for Tropical Medicine, 20359 Hamburg, Germany.|German Center for Infection Research (DZIF), Partner site Hamburg, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Günther
authors.affiliation: Institute for Neuropathology, University Medical Center Hamburg-Eppendorf, 20251 Hamburg, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Krasemann
authors.affiliation: Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Juliana
authors.initials: J
authors.lastname: Idoyaga
authors.affiliation: Department of Virology, Bernhard Nocht Institute for Tropical Medicine, 20359 Hamburg, Germany.|German Center for Infection Research (DZIF), Partner site Hamburg, Germany.
authors.forename: Lisa
authors.initials: L
authors.lastname: Oestereich
authors.affiliation: Heinrich Pette Institute, Leibniz Institute For Experimental Virology, Martinistrasse 52 20251 Hamburg, Germany.|Department of Virology, Bernhard Nocht Institute for Tropical Medicine, 20359 Hamburg, Germany.|German Center for Infection Research (DZIF), Partner site Hamburg, Germany.
authors.forename: César
authors.initials: C
authors.lastname: Muñoz-Fontela
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism; D039481:CD11b Antigen / Q000276:immunology / Q000378:metabolism; D045142:Cross-Priming / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism / Q000821:virology; D029043:Ebolavirus / Q000276:immunology* / Q000502:physiology; D019142:Hemorrhagic Fever, Ebola / Q000276:immunology* / Q000821:virology; D054884:Host-Pathogen Interactions / Q000276:immunology; D039001:Integrin alpha Chains / Q000276:immunology / Q000378:metabolism; D007700:Kinetics; D008221:Lymphoid Tissue / Q000276:immunology / Q000378:metabolism / Q000821:virology; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013601:T-Lymphocytes / Q000276:immunology*; D014766:Viremia / Q000276:immunology / Q000821:virology; D014779:Virus Replication / Q000276:immunology*
chemical_list: D015703:Antigens, CD; D039481:CD11b Antigen; D039001:Integrin alpha Chains; C091367:alpha E integrins