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

PLoS Pathog. 2022 Sep 26;18(9):e1010867. doi: 10.1371/journal.ppat.1010867. eCollection 2022 Sep.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin-Converting Enzyme 2 / genetics
  • Animals
  • COVID-19* / genetics
  • Disease Models, Animal
  • Gene Expression
  • Humans
  • Lung
  • Mice
  • Mice, Transgenic
  • Peptidyl-Dipeptidase A / metabolism
  • SARS-CoV-2 / genetics

Substances

  • Peptidyl-Dipeptidase A
  • Angiotensin-Converting Enzyme 2

Grant support

The SARS-CoV-2 PC3 work was supported by generous philanthropic donations from the Brazil Family Foundation (and many others). The project was also partly funded by an intramural seed grant from the Australian Infectious Diseases Research Centre. AS holds an Investigator grant from the National Health and Medical Research Council (NHMRC) of Australia (APP1173880). The funders played no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.