Inducible nitric oxide synthase deficiency promotes murine-ß-coronavirus induced demyelination.
Virol J
; 20(1): 51, 2023 03 25.
Article
in English
| MEDLINE | ID: covidwho-2265323
ABSTRACT
BACKGROUND:
Multiple sclerosis (MS) is characterized by neuroinflammation and demyelination orchestrated by activated neuroglial cells, CNS infiltrating leukocytes, and their reciprocal interactions through inflammatory signals. An inflammatory stimulus triggers inducible nitric oxide synthase (NOS2), a pro-inflammatory marker of microglia/macrophages (MG/Mφ) to catalyze sustained nitric oxide production. NOS2 during neuroinflammation, has been associated with MS disease pathology; however, studies dissecting its role in demyelination are limited. We studied the role of NOS2 in a recombinant ß-coronavirus-MHV-RSA59 induced neuroinflammation, an experimental animal model mimicking the pathological hallmarks of MS neuroinflammatory demyelination and axonal degeneration.OBJECTIVE:
Understanding the role of NOS2 in murine-ß-coronavirus-MHV-RSA59 demyelination.METHODS:
Brain and spinal cords from mock and RSA59 infected 4-5-week-old MHV-free C57BL/6 mice (WT) and NOS2-/- mice were harvested at different disease phases post infection (p.i.) (day 5/6-acute, day 9/10-acute-adaptive and day 30-chronic phase) and compared for pathological outcomes.RESULTS:
NOS2 was upregulated at the acute phase of RSA59-induced disease in WT mice and its deficiency resulted in severe disease and reduced survival at the acute-adaptive transition phase. Low survival in NOS2-/- mice was attributed to (i) high neuroinflammation resulting from increased accumulation of macrophages and neutrophils and (ii) Iba1 + phagocytic MG/Mφ mediated-early demyelination as observed at this phase. The phagocytic phenotype of CNS MG/Mφ was confirmed by significantly higher mRNA transcripts of phagocyte markers-CD206, TREM2, and Arg1 and double immunolabelling of Iba1 with MBP and PLP. Further, NOS2 deficiency led to exacerbated demyelination at the chronic phase as well.CONCLUSION:
Taken together the results imply that the immune system failed to control the disease progression in the absence of NOS2. Thus, our observations highlight a protective role of NOS2 in murine-ß-coronavirus induced demyelination.Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Demyelinating Diseases
/
Coronavirus Infections
/
Murine hepatitis virus
/
Nitric Oxide Synthase Type II
Type of study:
Observational study
/
Prognostic study
Limits:
Animals
Language:
English
Journal:
Virol J
Journal subject:
Virology
Year:
2023
Document Type:
Article
Affiliation country:
S12985-023-02006-1
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