SARS-CoV-2 pseudovirus dysregulates hematopoiesis and induces inflammaging of hematopoietic stem and progenitor cells
Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection primarily affects the respiratory system but may induce hematological alterations such as anemia, lymphopenia and thrombocytopenia. Previous studies have reported that SARS-CoV-2 efficiently infects hematopoietic stem an...
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Nature Publishing Group
2025-03-01
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| Series: | Experimental and Molecular Medicine |
| Online Access: | https://doi.org/10.1038/s12276-025-01416-1 |
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| author | Dong-Hoon Chae Hyun Sung Park Kyoung-Myeon Kim Aaron Yu Jae Han Park Mi-Kyung Oh Soon Won Choi Jaechul Ryu Cynthia E. Dunbar Hee Min Yoo Kyung-Rok Yu |
| author_facet | Dong-Hoon Chae Hyun Sung Park Kyoung-Myeon Kim Aaron Yu Jae Han Park Mi-Kyung Oh Soon Won Choi Jaechul Ryu Cynthia E. Dunbar Hee Min Yoo Kyung-Rok Yu |
| author_sort | Dong-Hoon Chae |
| collection | DOAJ |
| description | Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection primarily affects the respiratory system but may induce hematological alterations such as anemia, lymphopenia and thrombocytopenia. Previous studies have reported that SARS-CoV-2 efficiently infects hematopoietic stem and progenitor cells (HSPCs); however, the subsequent effects on hematopoiesis and immune reconstitution have not yet been described. Here we evaluated the pathological effects of infection of umbilical-cord-blood-derived HSPCs with the SARS-CoV-2 Omicron variant pseudovirus (PsV). Transcriptomic analysis of Omicron PsV-infected HSPCs revealed the upregulation of genes involved in inflammation, aging and the NLRP3 inflammasome, suggesting a potential trigger of inflammaging. Omicron PsV-infected HSPCs presented decreased numbers of multipotential progenitors (granulocyte‒erythrocyte‒macrophage‒megakaryocyte colony-forming units) ex vivo and repopulated primitive hematopoietic stem cells (Ki-67−hCD34+ cells) in an HSPC transplantation NOD-scid IL2rγnull mouse model (Omicron mouse). Furthermore, Omicron PsV infection induced myeloid-biased differentiation of HSPCs. Treatment with nanographene oxide, an antiviral agent, partially mitigated the myeloid bias and inflammaging phenotype both in vitro and in vivo. These findings provide insights into the abnormal hematopoietic and immune effects of SARS-CoV-2 infection and highlight potential therapeutic interventions. |
| format | Article |
| id | doaj-art-a2384bb370ac48a2ac36cf63fd9a7e99 |
| institution | OA Journals |
| issn | 2092-6413 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Experimental and Molecular Medicine |
| spelling | doaj-art-a2384bb370ac48a2ac36cf63fd9a7e992025-08-20T01:52:55ZengNature Publishing GroupExperimental and Molecular Medicine2092-64132025-03-0157361662710.1038/s12276-025-01416-1SARS-CoV-2 pseudovirus dysregulates hematopoiesis and induces inflammaging of hematopoietic stem and progenitor cellsDong-Hoon Chae0Hyun Sung Park1Kyoung-Myeon Kim2Aaron Yu3Jae Han Park4Mi-Kyung Oh5Soon Won Choi6Jaechul Ryu7Cynthia E. Dunbar8Hee Min Yoo9Kyung-Rok Yu10Department of Agricultural Biotechnology, Research Institute of Agriculture and Life Sciences, Seoul National UniversityDepartment of Agricultural Biotechnology, Research Institute of Agriculture and Life Sciences, Seoul National UniversityDepartment of Agricultural Biotechnology, Research Institute of Agriculture and Life Sciences, Seoul National UniversityDepartment of Agricultural Biotechnology, Research Institute of Agriculture and Life Sciences, Seoul National UniversityDepartment of Agricultural Biotechnology, Research Institute of Agriculture and Life Sciences, Seoul National UniversityDepartment of Agricultural Biotechnology, Research Institute of Agriculture and Life Sciences, Seoul National UniversityInstitutes of Convergence Technology, INBCTInstitutes of Convergence Technology, INBCTTranslational Stem Cell Biology Branch, National Heart, Lung, and Blood Institute, National Institutes of HealthBiometrology Group, Korea Research Institute of Standards and ScienceDepartment of Agricultural Biotechnology, Research Institute of Agriculture and Life Sciences, Seoul National UniversityAbstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection primarily affects the respiratory system but may induce hematological alterations such as anemia, lymphopenia and thrombocytopenia. Previous studies have reported that SARS-CoV-2 efficiently infects hematopoietic stem and progenitor cells (HSPCs); however, the subsequent effects on hematopoiesis and immune reconstitution have not yet been described. Here we evaluated the pathological effects of infection of umbilical-cord-blood-derived HSPCs with the SARS-CoV-2 Omicron variant pseudovirus (PsV). Transcriptomic analysis of Omicron PsV-infected HSPCs revealed the upregulation of genes involved in inflammation, aging and the NLRP3 inflammasome, suggesting a potential trigger of inflammaging. Omicron PsV-infected HSPCs presented decreased numbers of multipotential progenitors (granulocyte‒erythrocyte‒macrophage‒megakaryocyte colony-forming units) ex vivo and repopulated primitive hematopoietic stem cells (Ki-67−hCD34+ cells) in an HSPC transplantation NOD-scid IL2rγnull mouse model (Omicron mouse). Furthermore, Omicron PsV infection induced myeloid-biased differentiation of HSPCs. Treatment with nanographene oxide, an antiviral agent, partially mitigated the myeloid bias and inflammaging phenotype both in vitro and in vivo. These findings provide insights into the abnormal hematopoietic and immune effects of SARS-CoV-2 infection and highlight potential therapeutic interventions.https://doi.org/10.1038/s12276-025-01416-1 |
| spellingShingle | Dong-Hoon Chae Hyun Sung Park Kyoung-Myeon Kim Aaron Yu Jae Han Park Mi-Kyung Oh Soon Won Choi Jaechul Ryu Cynthia E. Dunbar Hee Min Yoo Kyung-Rok Yu SARS-CoV-2 pseudovirus dysregulates hematopoiesis and induces inflammaging of hematopoietic stem and progenitor cells Experimental and Molecular Medicine |
| title | SARS-CoV-2 pseudovirus dysregulates hematopoiesis and induces inflammaging of hematopoietic stem and progenitor cells |
| title_full | SARS-CoV-2 pseudovirus dysregulates hematopoiesis and induces inflammaging of hematopoietic stem and progenitor cells |
| title_fullStr | SARS-CoV-2 pseudovirus dysregulates hematopoiesis and induces inflammaging of hematopoietic stem and progenitor cells |
| title_full_unstemmed | SARS-CoV-2 pseudovirus dysregulates hematopoiesis and induces inflammaging of hematopoietic stem and progenitor cells |
| title_short | SARS-CoV-2 pseudovirus dysregulates hematopoiesis and induces inflammaging of hematopoietic stem and progenitor cells |
| title_sort | sars cov 2 pseudovirus dysregulates hematopoiesis and induces inflammaging of hematopoietic stem and progenitor cells |
| url | https://doi.org/10.1038/s12276-025-01416-1 |
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