title: Chimeric Mice with Competent Hematopoietic Immunity Reproduce Key Features of Severe Lassa Fever.
abstract: Lassa fever (LASF) is a highly severe viral syndrome endemic to West African countries. Despite the annual high morbidity and mortality caused by LASF, very little is known about the pathophysiology of the disease. Basic research on LASF has been precluded due to the lack of relevant small animal models that reproduce the human disease. Immunocompetent laboratory mice are resistant to infection with Lassa virus (LASV) and, to date, only immunodeficient mice, or mice expressing human HLA, have shown some degree of susceptibility to experimental infection. Here, transplantation of wild-type bone marrow cells into irradiated type I interferon receptor knockout mice (IFNAR-/-) was used to generate chimeric mice that reproduced important features of severe LASF in humans. This included high lethality, liver damage, vascular leakage and systemic virus dissemination. In addition, this model indicated that T cell-mediated immunopathology was an important component of LASF pathogenesis that was directly correlated with vascular leakage. Our strategy allows easy generation of a suitable small animal model to test new vaccines and antivirals and to dissect the basic components of LASF pathophysiology.
authors.affiliation: Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany.|German Center for Infection Research (DZIF), Partner Site Hamburg, Hamburg, Germany.
authors.forename: Lisa
authors.initials: L
authors.lastname: Oestereich
authors.affiliation: Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany.|German Center for Infection Research (DZIF), Partner Site Hamburg, Hamburg, Germany.|Heinrich Pette Institute, Leibniz Institute For Experimental Virology, Hamburg, Germany.
authors.forename: Anja
authors.initials: A
authors.lastname: Lüdtke
authors.affiliation: Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany.|German Center for Infection Research (DZIF), Partner Site Hamburg, Hamburg, Germany.|Heinrich Pette Institute, Leibniz Institute For Experimental Virology, Hamburg, Germany.
authors.forename: Paula
authors.initials: P
authors.lastname: Ruibal
authors.affiliation: Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany.|German Center for Infection Research (DZIF), Partner Site Hamburg, Hamburg, Germany.
authors.forename: Elisa
authors.initials: E
authors.lastname: Pallasch
authors.affiliation: Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany.|German Center for Infection Research (DZIF), Partner Site Hamburg, Hamburg, Germany.
authors.forename: Romy
authors.initials: R
authors.lastname: Kerber
authors.affiliation: Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany.|German Center for Infection Research (DZIF), Partner Site Hamburg, Hamburg, Germany.
authors.forename: Toni
authors.initials: T
authors.lastname: Rieger
authors.affiliation: Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany.|German Center for Infection Research (DZIF), Partner Site Hamburg, Hamburg, Germany.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Wurr
authors.affiliation: Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany.|German Center for Infection Research (DZIF), Partner Site Hamburg, Hamburg, Germany.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Bockholt
authors.affiliation: Heinrich Pette Institute, Leibniz Institute For Experimental Virology, Hamburg, Germany.
authors.forename: José V
authors.initials: JV
authors.lastname: Pérez-Girón
authors.affiliation: Institute for Neuropathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Krasemann
authors.affiliation: Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany.|German Center for Infection Research (DZIF), Partner Site Hamburg, Hamburg, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Günther
authors.affiliation: Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany.|German Center for Infection Research (DZIF), Partner Site Hamburg, Hamburg, Germany.|Heinrich Pette Institute, Leibniz Institute For Experimental Virology, Hamburg, Germany.
authors.forename: César
authors.initials: C
authors.lastname: Muñoz-Fontela
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005434:Flow Cytometry; D007150:Immunohistochemistry; D007835:Lassa Fever / Q000276:immunology* / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011828:Radiation Chimera