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Theiler's murine encephalomyelitis virus-induced cardiac and skeletal muscle disease
R M Gómez1, J E Rinehart, R Wollmann
1Department of Neurology, University of Chicago Pritzker School of Medicine, Illinois 60637, USA.
Abstract:
The DA strain of Theiler's murine encephalomyelitis virus, a member of the cardiovirus genus of picornaviruses, induces a restricted and persistent infection associated with a demyelinating process following intracerebral inoculation of mice; both virus infection and the immune response are believed to contribute to the late white matter disease. We now report that intraperitoneal inoculation with DA produces an acute myositis that progresses to a chronic inflammatory muscle disease in CD-1 mice as well as several inbred mouse strains. Some mouse strains also develop central nervous system white matter disease and a focal myocarditis. Infectious virus in skeletal muscle falls to undetectable levels 3 weeks postinoculation (p.i.), although viral genome persists for at least 12 weeks p.i., the longest period of observation. Severe combined immunodeficient animals have evidence of muscle pathology as long as 5 weeks p.i., suggesting that DA virus is capable of inducing chronic muscle disease in the absence of an immune response. The presence in immunocompetent mice, however, of prominent muscle inflammation in the absence of infectious virus suggests that the immune system also contributes to the pathology. T lymphocytes are the predominant cell type infiltrating the skeletal muscle during the chronic disease. This murine model may further our understanding of virus-induced chronic myositis and help to clarify the pathogenesis of human inflammatory myopathies.
Insights
Theiler's murine encephalomyelitis virus (TMEV) causes chronic muscle inflammation in mice, even without infectious virus. This suggests the immune system contributes to persistent myositis, offering a model for human inflammatory myopathies.
Area of Science:
- Virology
- Immunology
- Neurology
Background:
- Theiler's murine encephalomyelitis virus (TMEV) typically causes central nervous system demyelination.
- Previous studies suggest both viral infection and immune response contribute to TMEV-induced disease.
Purpose of the Study:
- To investigate the effects of intraperitoneal TMEV inoculation in mice.
- To characterize the development of chronic muscle disease and its underlying mechanisms.
Main Methods:
- Intraperitoneal inoculation of DA strain of TMEV in various mouse strains, including severe combined immunodeficient (SCID) mice.
- Monitoring of viral load (infectious virus and genome), muscle pathology, and immune cell infiltration over time (up to 12 weeks post-inoculation).
Main Results:
- Intraperitoneal TMEV inoculation induced acute myositis progressing to chronic inflammatory muscle disease in susceptible mice.
- Infectious TMEV became undetectable by 3 weeks post-inoculation, but viral genome persisted for at least 12 weeks.
- Muscle pathology was observed in SCID mice up to 5 weeks post-inoculation, indicating virus can induce chronic disease independently of adaptive immunity.
- In immunocompetent mice, chronic muscle inflammation occurred without detectable infectious virus, implicating the immune system, particularly T lymphocytes, in disease pathogenesis.
- Some mouse strains also developed central nervous system white matter disease and focal myocarditis.
Conclusions:
- TMEV infection can lead to chronic inflammatory muscle disease independent of persistent infectious virus.
- Both the virus and the host immune response, particularly T lymphocytes, contribute to the pathogenesis of chronic myositis.
- This TMEV-induced myositis model provides valuable insights into virus-induced chronic myopathies and the pathogenesis of human inflammatory myopathies.