Mouse models of COVID-19 recapitulate inflammatory pathways rather than gene expression.

Autor: Cameron R Bishop, Troy Dumenil, Daniel J Rawle, Thuy T Le, Kexin Yan, Bing Tang, Gunter Hartel, Andreas Suhrbier
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: PLoS Pathogens, Vol 18, Iss 9, p e1010867 (2022)
Druh dokumentu: article
ISSN: 1553-7366
1553-7374
DOI: 10.1371/journal.ppat.1010867
Popis: 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.
Databáze: Directory of Open Access Journals
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