A novel mouse model of SARS-CoV-2 induced neuroinflammation

ABSTRACT

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection may impact neurological function acutely or chronically, even in the absence of severe respiratory illness. Developing clinically relevant laboratory models to understand the neuropathogenesis of SARS-CoV-2 infection is an important step towards unravelling this neurologic consequence. We hypothesize that mouse adapted SARS-CoV-2 viral infection will induce neuroinflammation in immuno-competent C57BL/6J (10 weeks old male) as well as immunodeficient RAG2-/- (10 weeks old male) and BALB/c (1 year old female) mice. Method(s) All three mouse strains were inoculated intranasally with a dose of 1x103 PFU/mouse (50 microL) of either mock or the mouse-adapted (MA)10 strain of SARS-CoV-2 (BEI resource, NR-55329). Mice were euthanized on day 2, 3, 7, 15 or 30 post infection and brain samples processed for qRT-PCR, immunofluorescence, and H&E analysis. Result(s) SARS-CoV-2 MA10 resulted in a significantly higher (p < 0.05) mRNA expression for chemokine ligand 2 (CCL2) and lower (p < 0.05) mRNA expression for the blood-brain barrier component Claudin-5 in RAG2-/- and WT mice when compared to mock infection. Also, SARS-CoV-2 MA10 infection increased microglial expression in 1 year old female BALB/c mice after 2 days of infection, compared to mock infected group. At 30 days post infection, MA10 infected BALB/c mice had a higher perivascular lymphocyte cuffing in the brain. Conclusion(s) This study demonstrates that the mouse-adapted MA10 strain of SARS-CoV-2 can induce a neuroinflammatory state in the brain and more so in immunodeficient and aging mouse models. These mouse models will enable the investigation of the long-term neurological effects of SARS-CoV-2 infection. Copyright © 2022 the Alzheimer's Association.