Mouse Adapted SARS-CoV-2 (MA10) Viral Infection Induces Neuroinflammation in Standard Laboratory Mice

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  • Amruta, Narayanappa
    • Other Affiliation: Tulane University School of Medicine
  • Ismael, Saifudeen
    • Other Affiliation: Tulane University School of Medicine
  • Leist, Sarah R.
    • Affiliation: Gillings School of Global Public Health, Department of Epidemiology
  • Gressett, Timothy E.
    • Other Affiliation: Tulane University School of Medicine
  • Srivastava, Akhilesh
    • Other Affiliation: Tulane University School of Medicine
  • Dinnon III, Kenneth H.
    • Affiliation: Gillings School of Global Public Health, Department of Epidemiology
  • Engler-Chiurazzi, Elizabeth B.
    • Other Affiliation: Tulane University School of Medicine
  • Maness, Nicholas J.
    • Other Affiliation: Tulane University School of Medicine
  • Qin, Xuebin
    • Other Affiliation: Tulane University School of Medicine
  • Kolls, Jay K.
    • Other Affiliation: Tulane University School of Medicine
  • Baric, Ralph S.
    • Affiliation: Gillings School of Global Public Health, Department of Epidemiology
  • Bix, Gregory
    • Other Affiliation: Tulane University School of Medicine
Abstract
  • Increasing evidence suggests that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection impacts neurological function both acutely and chronically, even in the absence of pronounced respiratory distress. Developing clinically relevant laboratory mouse models of the neuropathogenesis of SARS-CoV-2 infection is an important step toward elucidating the underlying mechanisms of SARS-CoV-2-induced neurological dysfunction. Although various transgenic models and viral delivery methods have been used to study the infection potential of SARS-CoV-2 in mice, the use of commonly available laboratory mice would facilitate the study of SARS-CoV-2 neuropathology. Herein we show neuroinflammatory profiles of immunologically intact mice, C57BL/6J and BALB/c, as well as immunodeficient (Rag2−/−) mice, to a mouse-adapted strain of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2 (MA10)). Our findings indicate that brain IL-6 levels are significantly higher in BALB/c male mice infected with SARS-CoV-2 MA10. Additionally, blood-brain barrier integrity, as measured by the vascular tight junction protein claudin-5, was reduced by SARS-CoV-2 MA10 infection in all three strains. Brain glial fibrillary acidic protein (GFAP) mRNA was also elevated in male C57BL/6J infected mice compared with the mock group. Lastly, immune-vascular effects of SARS-CoV-2 (MA10), as measured by H&E scores, demonstrate an increase in perivascular lymphocyte cuffing (PLC) at 30 days post-infection among infected female BALB/c mice with a significant increase in PLC over time only in SARS-CoV-2 MA10) infected mice. Our study is the first to demonstrate that SARS-CoV-2 (MA10) infection induces neuroinflammation in laboratory mice and could be used as a novel model to study SARS-CoV-2-mediated cerebrovascular pathology.
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  • Article
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  • In Copyright
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  • Attribution 4.0 International
Journal title
  • Viruses
Journal volume
  • 15
Journal issue
  • 1
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  • English
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  • 1999-4915

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