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Chimeric Mice with Competent Hematopoietic Immunity Reproduce Key Features of Severe Lassa Fever

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 mo...

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Autores principales: Oestereich, Lisa, Lüdtke, Anja, Ruibal, Paula, Pallasch, Elisa, Kerber, Romy, Rieger, Toni, Wurr, Stephanie, Bockholt, Sabrina, Pérez-Girón, José V., Krasemann, Susanne, Günther, Stephan, Muñoz-Fontela, César
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4871546/
https://www.ncbi.nlm.nih.gov/pubmed/27191716
http://dx.doi.org/10.1371/journal.ppat.1005656
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author Oestereich, Lisa
Lüdtke, Anja
Ruibal, Paula
Pallasch, Elisa
Kerber, Romy
Rieger, Toni
Wurr, Stephanie
Bockholt, Sabrina
Pérez-Girón, José V.
Krasemann, Susanne
Günther, Stephan
Muñoz-Fontela, César
author_facet Oestereich, Lisa
Lüdtke, Anja
Ruibal, Paula
Pallasch, Elisa
Kerber, Romy
Rieger, Toni
Wurr, Stephanie
Bockholt, Sabrina
Pérez-Girón, José V.
Krasemann, Susanne
Günther, Stephan
Muñoz-Fontela, César
author_sort Oestereich, Lisa
collection PubMed
description 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.
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spelling pubmed-48715462016-05-31 Chimeric Mice with Competent Hematopoietic Immunity Reproduce Key Features of Severe Lassa Fever Oestereich, Lisa Lüdtke, Anja Ruibal, Paula Pallasch, Elisa Kerber, Romy Rieger, Toni Wurr, Stephanie Bockholt, Sabrina Pérez-Girón, José V. Krasemann, Susanne Günther, Stephan Muñoz-Fontela, César PLoS Pathog Research Article 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. Public Library of Science 2016-05-18 /pmc/articles/PMC4871546/ /pubmed/27191716 http://dx.doi.org/10.1371/journal.ppat.1005656 Text en © 2016 Oestereich et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Oestereich, Lisa
Lüdtke, Anja
Ruibal, Paula
Pallasch, Elisa
Kerber, Romy
Rieger, Toni
Wurr, Stephanie
Bockholt, Sabrina
Pérez-Girón, José V.
Krasemann, Susanne
Günther, Stephan
Muñoz-Fontela, César
Chimeric Mice with Competent Hematopoietic Immunity Reproduce Key Features of Severe Lassa Fever
title Chimeric Mice with Competent Hematopoietic Immunity Reproduce Key Features of Severe Lassa Fever
title_full Chimeric Mice with Competent Hematopoietic Immunity Reproduce Key Features of Severe Lassa Fever
title_fullStr Chimeric Mice with Competent Hematopoietic Immunity Reproduce Key Features of Severe Lassa Fever
title_full_unstemmed Chimeric Mice with Competent Hematopoietic Immunity Reproduce Key Features of Severe Lassa Fever
title_short Chimeric Mice with Competent Hematopoietic Immunity Reproduce Key Features of Severe Lassa Fever
title_sort chimeric mice with competent hematopoietic immunity reproduce key features of severe lassa fever
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4871546/
https://www.ncbi.nlm.nih.gov/pubmed/27191716
http://dx.doi.org/10.1371/journal.ppat.1005656
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