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

Area of Science:

• Neuroscience
• Immunology
• Virology

Background:

• Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is increasingly linked to neurological dysfunction.
• Developing mouse models is crucial for understanding SARS-CoV-2 neuropathogenesis.
• Existing models often use transgenic mice or complex delivery methods, limiting accessibility.

Purpose of the Study:

• To investigate the neuroinflammatory profiles of commonly available laboratory mice infected with a mouse-adapted SARS-CoV-2 strain (MA10).
• To assess the impact of SARS-CoV-2 (MA10) on blood-brain barrier integrity and neuroinflammation markers.
• To establish a relevant mouse model for studying SARS-CoV-2-mediated cerebrovascular pathology.

Main Methods:

• Infection of C57BL/6J, BALB/c, and immunodeficient (Rag2-/-) mice with SARS-CoV-2 (MA10).
• Measurement of brain IL-6 levels and glial fibrillary acidic protein (GFAP) mRNA.
• Assessment of blood-brain barrier integrity via claudin-5 expression.
• Histopathological analysis (H&E staining) for perivascular lymphocyte cuffing (PLC).

Main Results:

• SARS-CoV-2 (MA10) infection elevated brain IL-6 levels in BALB/c male mice.
• Reduced blood-brain barrier integrity (claudin-5) was observed across all infected mouse strains.
• Elevated GFAP mRNA in male C57BL/6J mice and increased perivascular lymphocyte cuffing in female BALB/c mice over time were noted.
• The study demonstrated neuroinflammation and immune-vascular effects in infected mice.

Conclusions:

• SARS-CoV-2 (MA10) infection induces significant neuroinflammation and cerebrovascular pathology in laboratory mice.
• This mouse model offers a valuable tool for investigating SARS-CoV-2-related neurological complications.
• The findings highlight the potential for SARS-CoV-2 to impact the central nervous system even without severe respiratory symptoms.