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Chikungunya patient transcriptional signatures faithfully recapitulated in a C57BL/6J mouse model

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  • 06/25/2025
Type of Material
Authors
    Cameron R Bishop, Berghofer Medical Research InstituteFelipe Ten Caten, Emory UniversityHelder Nakaya, Emory UniversityAndreas Suhrbier, Berghofer Medical Research Institute
Language
  • English
Date
  • 2022-12-12
Publisher
  • Frontiers Media
Publication Version
Copyright Statement
  • © 2022 Bishop, Caten, Nakaya and Suhrbier
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Final Published Version (URL)
Title of Journal or Parent Work
Volume
  • 13
Grant/Funding Information
  • HN and FC received support by Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) (2018/14933-2), Brazil.
  • The work was supported by an Investigator grant from the National Health and Medical Research Council (NHMRC) of Australia (APP1173880) awarded to AS.
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Abstract
  • Introduction An adult wild-type C57BL/6J mouse model of chikungunya virus (CHIKV) infection and disease has been extensively used to study the alphaviral arthritic immunopathology and to evaluate new interventions. How well mouse models recapitulate the gene expression profiles seen in humans remains controversial. Methods Herein we perform a comparative transcriptomics analysis using RNA-Seq datasets from the C57BL/6J CHIKV mouse model with datasets obtained from adults and children acutely infected with CHIKV. Results Despite sampling quite different tissues, peripheral blood from humans and feet from mice, gene expression profiles were quite similar, with an overlap of up to ≈50% for up-regulated single copy orthologue differentially expressed genes. Furthermore, high levels of significant concordance between mouse and human were seen for immune pathways and signatures, which were dominated by interferons, T cells and monocyte/macrophages. Importantly, predicted responses to a series of anti-inflammatory drug and biologic treatments also showed cogent similarities between species. Discussion Comparative transcriptomics and subsequent pathway analysis provides a detailed picture of how a given model recapitulates human gene expression. Using this method, we show that the C57BL/6J CHIKV mouse model provides a reliable and representative system in which to study CHIKV immunopathology and evaluate new treatments.
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  • Health Sciences, Medicine and Surgery

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