Chimeric Mice with Competent Hematopoietic Immunity Reproduce Key Features of Severe Lassa Fever
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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.
In: PLOS PATHOG, Vol. 12, No. 5, 05.2016, p. e1005656.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Chimeric Mice with Competent Hematopoietic Immunity Reproduce Key Features of Severe Lassa Fever
AU - Oestereich, Lisa
AU - Lüdtke, Anja
AU - Ruibal, Paula
AU - Pallasch, Elisa
AU - Kerber, Romy
AU - Rieger, Toni
AU - Wurr, Stephanie
AU - Bockholt, Sabrina
AU - Pérez-Girón, José V
AU - Krasemann, Susanne
AU - Günther, Stephan
AU - Muñoz-Fontela, César
PY - 2016/5
Y1 - 2016/5
N2 - 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.
AB - 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.
U2 - 10.1371/journal.ppat.1005656
DO - 10.1371/journal.ppat.1005656
M3 - SCORING: Journal article
C2 - 27191716
VL - 12
SP - e1005656
JO - PLOS PATHOG
JF - PLOS PATHOG
SN - 1553-7366
IS - 5
ER -
