SARS-CoV-2 variants induce distinct disease and impact in the bone marrow and thymus of mice
Summary: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has evolved to variants associated with milder disease. We employed the k18-hACE2 mouse model to study how differences in the course of infection by SARS-CoV-2 variants alpha, delta, and omicron relate to tissue pathology and the...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-02-01
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| Series: | iScience |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004223000494 |
| _version_ | 1797903369140961280 |
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| author | Rute Gonçalves Joana Couto Pedro Ferreirinha José Maria Costa Diogo Silvério Marta L. Silva Ana Isabel Fernandes Pedro Madureira Nuno L. Alves Sofia Lamas Margarida Saraiva |
| author_facet | Rute Gonçalves Joana Couto Pedro Ferreirinha José Maria Costa Diogo Silvério Marta L. Silva Ana Isabel Fernandes Pedro Madureira Nuno L. Alves Sofia Lamas Margarida Saraiva |
| author_sort | Rute Gonçalves |
| collection | DOAJ |
| description | Summary: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has evolved to variants associated with milder disease. We employed the k18-hACE2 mouse model to study how differences in the course of infection by SARS-CoV-2 variants alpha, delta, and omicron relate to tissue pathology and the immune response triggered. We documented a variant-specific pattern of infection severity, inducing discrete lung and blood immune responses and differentially impacting primary lymphoid organs. Infections with variants alpha and delta promoted bone marrow (BM) emergency myelopoiesis, with blood and lung neutrophilia. The defects in the BM hematopoietic compartment extended to the thymus, with the infection by the alpha variant provoking a marked thymic atrophy. Importantly, the changes in the immune responses correlated with the severity of infection. Our study provides a comprehensive platform to investigate the modulation of disease by SARS-CoV-2 variants and underscores the impact of this infection on the function of primary lymphoid organs. |
| first_indexed | 2024-04-10T09:31:48Z |
| format | Article |
| id | doaj.art-3d37c31a0cb84333b741b667787563b0 |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-04-10T09:31:48Z |
| publishDate | 2023-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-3d37c31a0cb84333b741b667787563b02023-02-19T04:26:46ZengElsevieriScience2589-00422023-02-01262105972SARS-CoV-2 variants induce distinct disease and impact in the bone marrow and thymus of miceRute Gonçalves0Joana Couto1Pedro Ferreirinha2José Maria Costa3Diogo Silvério4Marta L. Silva5Ana Isabel Fernandes6Pedro Madureira7Nuno L. Alves8Sofia Lamas9Margarida Saraiva10i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, 4200-135 Porto, Portugali3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, 4200-135 Porto, Portugali3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, 4200-135 Porto, Portugal; IBMC—Instituto de Biologia Molecular e Celular, Universidade do Porto, 4200-135 Porto, Portugali3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, 4200-135 Porto, Portugal; FEUP—Faculdade de Engenharia, Universidade do Porto, 4200-465 Porto, Portugali3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, 4200-135 Porto, Portugal; ICBAS—Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, 4050-313 Porto, Portugali3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, 4200-135 Porto, Portugal; ICBAS—Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, 4050-313 Porto, Portugali3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, 4200-135 Porto, Portugal; ICBAS—Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, 4050-313 Porto, Portugali3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, 4200-135 Porto, Portugal; Immunethep, Biocant Park, 3060-197 Cantanhede, Portugali3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, 4200-135 Porto, Portugal; IBMC—Instituto de Biologia Molecular e Celular, Universidade do Porto, 4200-135 Porto, Portugali3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, 4200-135 Porto, Portugal; IBMC—Instituto de Biologia Molecular e Celular, Universidade do Porto, 4200-135 Porto, Portugali3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, 4200-135 Porto, Portugal; IBMC—Instituto de Biologia Molecular e Celular, Universidade do Porto, 4200-135 Porto, Portugal; Corresponding authorSummary: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has evolved to variants associated with milder disease. We employed the k18-hACE2 mouse model to study how differences in the course of infection by SARS-CoV-2 variants alpha, delta, and omicron relate to tissue pathology and the immune response triggered. We documented a variant-specific pattern of infection severity, inducing discrete lung and blood immune responses and differentially impacting primary lymphoid organs. Infections with variants alpha and delta promoted bone marrow (BM) emergency myelopoiesis, with blood and lung neutrophilia. The defects in the BM hematopoietic compartment extended to the thymus, with the infection by the alpha variant provoking a marked thymic atrophy. Importantly, the changes in the immune responses correlated with the severity of infection. Our study provides a comprehensive platform to investigate the modulation of disease by SARS-CoV-2 variants and underscores the impact of this infection on the function of primary lymphoid organs.http://www.sciencedirect.com/science/article/pii/S2589004223000494PathologyImmunologyComponents of the immune systemVirology |
| spellingShingle | Rute Gonçalves Joana Couto Pedro Ferreirinha José Maria Costa Diogo Silvério Marta L. Silva Ana Isabel Fernandes Pedro Madureira Nuno L. Alves Sofia Lamas Margarida Saraiva SARS-CoV-2 variants induce distinct disease and impact in the bone marrow and thymus of mice iScience Pathology Immunology Components of the immune system Virology |
| title | SARS-CoV-2 variants induce distinct disease and impact in the bone marrow and thymus of mice |
| title_full | SARS-CoV-2 variants induce distinct disease and impact in the bone marrow and thymus of mice |
| title_fullStr | SARS-CoV-2 variants induce distinct disease and impact in the bone marrow and thymus of mice |
| title_full_unstemmed | SARS-CoV-2 variants induce distinct disease and impact in the bone marrow and thymus of mice |
| title_short | SARS-CoV-2 variants induce distinct disease and impact in the bone marrow and thymus of mice |
| title_sort | sars cov 2 variants induce distinct disease and impact in the bone marrow and thymus of mice |
| topic | Pathology Immunology Components of the immune system Virology |
| url | http://www.sciencedirect.com/science/article/pii/S2589004223000494 |
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