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...
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2016-05-01
|
| Series: | PLoS Pathogens |
| Online Access: | https://doi.org/10.1371/journal.ppat.1005656 |
| _version_ | 1819133114095501312 |
|---|---|
| author | Lisa Oestereich Anja Lüdtke Paula Ruibal Elisa Pallasch Romy Kerber Toni Rieger Stephanie Wurr Sabrina Bockholt José V Pérez-Girón Susanne Krasemann Stephan Günther César Muñoz-Fontela |
| author_facet | Lisa Oestereich Anja Lüdtke Paula Ruibal Elisa Pallasch Romy Kerber Toni Rieger Stephanie Wurr Sabrina Bockholt José V Pérez-Girón Susanne Krasemann Stephan Günther César Muñoz-Fontela |
| author_sort | Lisa Oestereich |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-22T09:42:09Z |
| format | Article |
| id | doaj.art-2e96e73976054345b754842ce5c740ff |
| institution | Directory Open Access Journal |
| issn | 1553-7366 1553-7374 |
| language | English |
| last_indexed | 2024-12-22T09:42:09Z |
| publishDate | 2016-05-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj.art-2e96e73976054345b754842ce5c740ff2022-12-21T18:30:38ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742016-05-01125e100565610.1371/journal.ppat.1005656Chimeric Mice with Competent Hematopoietic Immunity Reproduce Key Features of Severe Lassa Fever.Lisa OestereichAnja LüdtkePaula RuibalElisa PallaschRomy KerberToni RiegerStephanie WurrSabrina BockholtJosé V Pérez-GirónSusanne KrasemannStephan GüntherCésar Muñoz-FontelaLassa 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.https://doi.org/10.1371/journal.ppat.1005656 |
| spellingShingle | Lisa Oestereich Anja Lüdtke Paula Ruibal Elisa Pallasch Romy Kerber Toni Rieger Stephanie Wurr Sabrina Bockholt José V Pérez-Girón Susanne Krasemann Stephan Günther César Muñoz-Fontela Chimeric Mice with Competent Hematopoietic Immunity Reproduce Key Features of Severe Lassa Fever. PLoS Pathogens |
| 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 |
| url | https://doi.org/10.1371/journal.ppat.1005656 |
| work_keys_str_mv | AT lisaoestereich chimericmicewithcompetenthematopoieticimmunityreproducekeyfeaturesofseverelassafever AT anjaludtke chimericmicewithcompetenthematopoieticimmunityreproducekeyfeaturesofseverelassafever AT paularuibal chimericmicewithcompetenthematopoieticimmunityreproducekeyfeaturesofseverelassafever AT elisapallasch chimericmicewithcompetenthematopoieticimmunityreproducekeyfeaturesofseverelassafever AT romykerber chimericmicewithcompetenthematopoieticimmunityreproducekeyfeaturesofseverelassafever AT tonirieger chimericmicewithcompetenthematopoieticimmunityreproducekeyfeaturesofseverelassafever AT stephaniewurr chimericmicewithcompetenthematopoieticimmunityreproducekeyfeaturesofseverelassafever AT sabrinabockholt chimericmicewithcompetenthematopoieticimmunityreproducekeyfeaturesofseverelassafever AT josevperezgiron chimericmicewithcompetenthematopoieticimmunityreproducekeyfeaturesofseverelassafever AT susannekrasemann chimericmicewithcompetenthematopoieticimmunityreproducekeyfeaturesofseverelassafever AT stephangunther chimericmicewithcompetenthematopoieticimmunityreproducekeyfeaturesofseverelassafever AT cesarmunozfontela chimericmicewithcompetenthematopoieticimmunityreproducekeyfeaturesofseverelassafever |