A pan-orthohantavirus human lung xenograft mouse model and its utility for preclinical studies.
Orthohantaviruses are emerging zoonotic viruses that can infect humans via the respiratory tract. There is an unmet need for an in vivo model to study infection of different orthohantaviruses in physiologically relevant tissue and to assess the efficacy of novel pan-orthohantavirus countermeasures....
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| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2025-01-01
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| Series: | PLoS Pathogens |
| Online Access: | https://doi.org/10.1371/journal.ppat.1012875 |
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| author | Melanie Rissmann Danny Noack Thomas M Spliethof Vincent P Vaes Rianne Stam Peter van Run Jordan J Clark Georges M G M Verjans Bart L Haagmans Florian Krammer Marion P G Koopmans Judith M A van den Brand Barry Rockx |
| author_facet | Melanie Rissmann Danny Noack Thomas M Spliethof Vincent P Vaes Rianne Stam Peter van Run Jordan J Clark Georges M G M Verjans Bart L Haagmans Florian Krammer Marion P G Koopmans Judith M A van den Brand Barry Rockx |
| author_sort | Melanie Rissmann |
| collection | DOAJ |
| description | Orthohantaviruses are emerging zoonotic viruses that can infect humans via the respiratory tract. There is an unmet need for an in vivo model to study infection of different orthohantaviruses in physiologically relevant tissue and to assess the efficacy of novel pan-orthohantavirus countermeasures. Here, we describe the use of a human lung xenograft mouse model to study the permissiveness for different orthohantavirus species and to assess its utility for preclinical testing of therapeutics. Following infection of xenografted human lung tissues, distinct orthohantavirus species differentially replicated in the human lung and subsequently spread systemically. The different orthohantaviruses primarily targeted the endothelium, respiratory epithelium and macrophages in the human lung. A proof-of-concept preclinical study showed treatment of these mice with a virus neutralizing antibody could block Andes orthohantavirus infection and dissemination. This pan-orthohantavirus model will facilitate progress in the fundamental understanding of pathogenesis and virus-host interactions for orthohantaviruses. Furthermore, it is an invaluable tool for preclinical evaluation of novel candidate pan-orthohantavirus intervention strategies. |
| format | Article |
| id | doaj-art-4915898e0e1a416080378f3d295cb33b |
| institution | Kabale University |
| issn | 1553-7366 1553-7374 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj-art-4915898e0e1a416080378f3d295cb33b2025-02-05T05:30:53ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742025-01-01211e101287510.1371/journal.ppat.1012875A pan-orthohantavirus human lung xenograft mouse model and its utility for preclinical studies.Melanie RissmannDanny NoackThomas M SpliethofVincent P VaesRianne StamPeter van RunJordan J ClarkGeorges M G M VerjansBart L HaagmansFlorian KrammerMarion P G KoopmansJudith M A van den BrandBarry RockxOrthohantaviruses are emerging zoonotic viruses that can infect humans via the respiratory tract. There is an unmet need for an in vivo model to study infection of different orthohantaviruses in physiologically relevant tissue and to assess the efficacy of novel pan-orthohantavirus countermeasures. Here, we describe the use of a human lung xenograft mouse model to study the permissiveness for different orthohantavirus species and to assess its utility for preclinical testing of therapeutics. Following infection of xenografted human lung tissues, distinct orthohantavirus species differentially replicated in the human lung and subsequently spread systemically. The different orthohantaviruses primarily targeted the endothelium, respiratory epithelium and macrophages in the human lung. A proof-of-concept preclinical study showed treatment of these mice with a virus neutralizing antibody could block Andes orthohantavirus infection and dissemination. This pan-orthohantavirus model will facilitate progress in the fundamental understanding of pathogenesis and virus-host interactions for orthohantaviruses. Furthermore, it is an invaluable tool for preclinical evaluation of novel candidate pan-orthohantavirus intervention strategies.https://doi.org/10.1371/journal.ppat.1012875 |
| spellingShingle | Melanie Rissmann Danny Noack Thomas M Spliethof Vincent P Vaes Rianne Stam Peter van Run Jordan J Clark Georges M G M Verjans Bart L Haagmans Florian Krammer Marion P G Koopmans Judith M A van den Brand Barry Rockx A pan-orthohantavirus human lung xenograft mouse model and its utility for preclinical studies. PLoS Pathogens |
| title | A pan-orthohantavirus human lung xenograft mouse model and its utility for preclinical studies. |
| title_full | A pan-orthohantavirus human lung xenograft mouse model and its utility for preclinical studies. |
| title_fullStr | A pan-orthohantavirus human lung xenograft mouse model and its utility for preclinical studies. |
| title_full_unstemmed | A pan-orthohantavirus human lung xenograft mouse model and its utility for preclinical studies. |
| title_short | A pan-orthohantavirus human lung xenograft mouse model and its utility for preclinical studies. |
| title_sort | pan orthohantavirus human lung xenograft mouse model and its utility for preclinical studies |
| url | https://doi.org/10.1371/journal.ppat.1012875 |
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