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Activation of glial cells by human coronavirus OC43 infection
J A Edwards1, F Denis, P J Talbot
1Laboratory of Neuroimmunovirology, Human Health Research Center, INRS-Institut Armand-Frappier, Université du Québec, 531 Boulevard des Prairies, Québec, H7V 1B7, Laval, Canada.
Abstract:
Multiple sclerosis (MS) is an immune-mediated demyelinating disease that could be triggered by a viral infection. Coronaviruses induce an MS-like disease in rodents, are neuroinvasive in humans and can infect primary cultures of human astrocytes and microglia. Infection of the human astrocytic cell line U-373MG by the OC43 strain of human coronavirus caused an upregulation of IL-6, TNF-alpha, and MCP-1 mRNA expression. This virus also modulated the activity of matrix metalloproteinases-2 and -9 and augmented nitric oxide production in both U-373MG cells and the human microglial cell line CHME-5. Thus, a coronaviral infection of glial cells could lead to the production of inflammatory molecules that have been associated with central nervous system pathologies such as MS.
Insights
Human coronavirus OC43 infection of glial cells increases inflammatory molecules linked to multiple sclerosis (MS). This suggests a potential viral trigger for MS pathogenesis, impacting astrocytes and microglia.
Area of Science:
- Neuroimmunology
- Virology
- Cellular Pathology
Background:
- Multiple sclerosis (MS) is an immune-mediated demyelinating disease.
- Viral infections are potential triggers for MS.
- Coronaviruses are neuroinvasive and can infect human glial cells.
Purpose of the Study:
- To investigate the effect of human coronavirus OC43 on glial cells.
- To determine if coronavirus infection induces inflammatory responses relevant to MS.
Main Methods:
- Infection of human astrocytic (U-373MG) and microglial (CHME-5) cell lines with human coronavirus OC43.
- Analysis of mRNA expression for inflammatory cytokines (IL-6, TNF-alpha, MCP-1).
- Assessment of matrix metalloproteinase (MMP-2, MMP-9) activity and nitric oxide production.
Main Results:
- Human coronavirus OC43 infection upregulated IL-6, TNF-alpha, and MCP-1 mRNA in U-373MG cells.
- The virus modulated MMP-2 and MMP-9 activity in both cell lines.
- Nitric oxide production was augmented in infected U-373MG and CHME-5 cells.
Conclusions:
- Coronaviral infection of human glial cells leads to the production of key inflammatory molecules.
- These inflammatory mediators are associated with central nervous system pathologies, including MS.
- Coronaviruses represent a potential etiological factor in MS development.