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Inhibition of virus-induced age-dependent poliomyelitis by interferon-gamma
W A Cafruny1, T R Haven, S R Lawson
1Department of Microbiology, University of South Dakota School of Medicine, Vermillion, USA. bcafruny@sundance.usd.edu
Abstract:
Age-dependent poliomyelitis (ADPM) is a neuroparolytic disease which results from combined infection of susceptible mice with lactate dehydrogenase-elevating virus (LDV) and murine leukemia virus (MuLV). The present study examined the effects of interferon-gamma (IFN-gamma) treatment on the incidence of ADPM, replication of LDV and MuLV and anti-LDV immunity. IFN-gamma treatment of ADPM-susceptible C58/M mice protected them from paralytic disease, but had no detectable effect on the IgG anti-LDV response or LDV viremia. IFN-gamma-mediated protection from ADPM correlated with reduced expression of LDV RNA, but not MuLV RNA, in the spinal cords of C58/M mice. These results confirm that spinal cord LDV replication is the determinant of ADPM and demonstrate that cytokine-mediated inhibition of LDV replication in the central nervous system prevents neuroparalytic disease.
Insights
Interferon-gamma (IFN-gamma) prevents age-dependent poliomyelitis (ADPM) in mice by inhibiting lactate dehydrogenase-elevating virus (LDV) replication in the spinal cord. This cytokine treatment offers protection without affecting anti-LDV immunity or viremia.
Area of Science:
- Virology
- Immunology
- Neuroscience
Background:
- Age-dependent poliomyelitis (ADPM) is a neuroparalytic condition caused by co-infection with lactate dehydrogenase-elevating virus (LDV) and murine leukemia virus (MuLV).
- Understanding the mechanisms of ADPM pathogenesis and potential therapeutic interventions is crucial for managing neuroinflammatory diseases.
Purpose of the Study:
- To investigate the therapeutic effects of interferon-gamma (IFN-gamma) on ADPM incidence.
- To assess the impact of IFN-gamma on LDV and MuLV replication and anti-LDV immune responses.
Main Methods:
- Treatment of ADPM-susceptible C58/M mice with IFN-gamma.
- Monitoring of ADPM incidence, viral RNA expression in spinal cords, and IgG anti-LDV antibody levels.
- Quantification of LDV and MuLV RNA in the central nervous system.
Main Results:
- IFN-gamma treatment protected mice from paralytic ADPM.
- Protection correlated with reduced LDV RNA expression in the spinal cord, but not MuLV RNA.
- IFN-gamma did not affect LDV viremia or the IgG anti-LDV immune response.
Conclusions:
- Spinal cord LDV replication is the critical determinant of ADPM.
- Cytokine-mediated inhibition of LDV replication in the CNS can prevent neuroparalytic disease.
- IFN-gamma represents a potential therapeutic strategy for ADPM by targeting viral replication in the CNS.
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