Mouse models of COVID-19 recapitulate inflammatory pathways rather than gene expression.
How well mouse models recapitulate the transcriptional profiles seen in humans remains debatable, with both conservation and diversity identified in various settings. Herein we use RNA-Seq data and bioinformatics approaches to analyze the transcriptional responses in SARS-CoV-2 infected lungs, compa...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2022-09-01
|
| Series: | PLoS Pathogens |
| Online Access: | https://doi.org/10.1371/journal.ppat.1010867 |
| _version_ | 1811329278829133824 |
|---|---|
| author | Cameron R Bishop Troy Dumenil Daniel J Rawle Thuy T Le Kexin Yan Bing Tang Gunter Hartel Andreas Suhrbier |
| author_facet | Cameron R Bishop Troy Dumenil Daniel J Rawle Thuy T Le Kexin Yan Bing Tang Gunter Hartel Andreas Suhrbier |
| author_sort | Cameron R Bishop |
| collection | DOAJ |
| description | How well mouse models recapitulate the transcriptional profiles seen in humans remains debatable, with both conservation and diversity identified in various settings. Herein we use RNA-Seq data and bioinformatics approaches to analyze the transcriptional responses in SARS-CoV-2 infected lungs, comparing 4 human studies with the widely used K18-hACE2 mouse model, a model where hACE2 is expressed from the mouse ACE2 promoter, and a model that uses a mouse adapted virus and wild-type mice. Overlap of single copy orthologue differentially expressed genes (scoDEGs) between human and mouse studies was generally poor (≈15-35%). Rather than being associated with batch, sample treatment, viral load, lung damage or mouse model, the poor overlaps were primarily due to scoDEG expression differences between species. Importantly, analyses of immune signatures and inflammatory pathways illustrated highly significant concordances between species. As immunity and immunopathology are the focus of most studies, these mouse models can thus be viewed as representative and relevant models of COVID-19. |
| first_indexed | 2024-04-13T15:40:59Z |
| format | Article |
| id | doaj.art-a1b4187f3c6b4ab09dc55588b8b10abd |
| institution | Directory Open Access Journal |
| issn | 1553-7366 1553-7374 |
| language | English |
| last_indexed | 2024-04-13T15:40:59Z |
| publishDate | 2022-09-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj.art-a1b4187f3c6b4ab09dc55588b8b10abd2022-12-22T02:41:08ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742022-09-01189e101086710.1371/journal.ppat.1010867Mouse models of COVID-19 recapitulate inflammatory pathways rather than gene expression.Cameron R BishopTroy DumenilDaniel J RawleThuy T LeKexin YanBing TangGunter HartelAndreas SuhrbierHow well mouse models recapitulate the transcriptional profiles seen in humans remains debatable, with both conservation and diversity identified in various settings. Herein we use RNA-Seq data and bioinformatics approaches to analyze the transcriptional responses in SARS-CoV-2 infected lungs, comparing 4 human studies with the widely used K18-hACE2 mouse model, a model where hACE2 is expressed from the mouse ACE2 promoter, and a model that uses a mouse adapted virus and wild-type mice. Overlap of single copy orthologue differentially expressed genes (scoDEGs) between human and mouse studies was generally poor (≈15-35%). Rather than being associated with batch, sample treatment, viral load, lung damage or mouse model, the poor overlaps were primarily due to scoDEG expression differences between species. Importantly, analyses of immune signatures and inflammatory pathways illustrated highly significant concordances between species. As immunity and immunopathology are the focus of most studies, these mouse models can thus be viewed as representative and relevant models of COVID-19.https://doi.org/10.1371/journal.ppat.1010867 |
| spellingShingle | Cameron R Bishop Troy Dumenil Daniel J Rawle Thuy T Le Kexin Yan Bing Tang Gunter Hartel Andreas Suhrbier Mouse models of COVID-19 recapitulate inflammatory pathways rather than gene expression. PLoS Pathogens |
| title | Mouse models of COVID-19 recapitulate inflammatory pathways rather than gene expression. |
| title_full | Mouse models of COVID-19 recapitulate inflammatory pathways rather than gene expression. |
| title_fullStr | Mouse models of COVID-19 recapitulate inflammatory pathways rather than gene expression. |
| title_full_unstemmed | Mouse models of COVID-19 recapitulate inflammatory pathways rather than gene expression. |
| title_short | Mouse models of COVID-19 recapitulate inflammatory pathways rather than gene expression. |
| title_sort | mouse models of covid 19 recapitulate inflammatory pathways rather than gene expression |
| url | https://doi.org/10.1371/journal.ppat.1010867 |
| work_keys_str_mv | AT cameronrbishop mousemodelsofcovid19recapitulateinflammatorypathwaysratherthangeneexpression AT troydumenil mousemodelsofcovid19recapitulateinflammatorypathwaysratherthangeneexpression AT danieljrawle mousemodelsofcovid19recapitulateinflammatorypathwaysratherthangeneexpression AT thuytle mousemodelsofcovid19recapitulateinflammatorypathwaysratherthangeneexpression AT kexinyan mousemodelsofcovid19recapitulateinflammatorypathwaysratherthangeneexpression AT bingtang mousemodelsofcovid19recapitulateinflammatorypathwaysratherthangeneexpression AT gunterhartel mousemodelsofcovid19recapitulateinflammatorypathwaysratherthangeneexpression AT andreassuhrbier mousemodelsofcovid19recapitulateinflammatorypathwaysratherthangeneexpression |