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RNase L mediated protection from virus induced demyelination.

PLoS pathogens, ISSN: 1553-7374, Vol: 5, Issue: 10, Page: e1000602
2009
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Article Description

IFN-alpha/beta plays a critical role in limiting viral spread, restricting viral tropism and protecting mice from neurotropic coronavirus infection. However, the IFN-alpha/beta dependent mechanisms underlying innate anti-viral functions within the CNS are poorly understood. The role of RNase L in viral encephalomyelitis was explored based on its functions in inhibiting translation, inducing apoptosis, and propagating the IFN-alpha/beta pathway through RNA degradation intermediates. Infection of RNase L deficient (RL(-/-)) mice with a sub-lethal, demyelinating mouse hepatitis virus variant revealed that the majority of mice succumbed to infection by day 12 p.i. However, RNase L deficiency did not affect overall control of infectious virus, or diminish IFN-alpha/beta expression in the CNS. Furthermore, increased morbidity and mortality could not be attributed to altered proinflammatory signals or composition of cells infiltrating the CNS. The unique phenotype of infected RL(-/-) mice was rather manifested in earlier onset and increased severity of demyelination and axonal damage in brain stem and spinal cord without evidence for enhanced neuronal infection. Increased tissue damage coincided with sustained brain stem infection, foci of microglia infection in grey matter, and increased apoptotic cells. These data demonstrate a novel protective role for RNase L in viral induced CNS encephalomyelitis, which is not reflected in overall viral control or propagation of IFN-alpha/beta mediated signals. Protective function is rather associated with cell type specific and regional restriction of viral replication in grey matter and ameliorated neurodegeneration and demyelination.

Bibliographic Details

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Derek D. C. Ireland; Stephen A. Stohlman; David R. Hinton; Parul Kapil; Robert H. Silverman; Roscoe A. Atkinson; Cornelia C. Bergmann; Glenn F. Rall

Public Library of Science (PLoS)

Immunology and Microbiology; Biochemistry, Genetics and Molecular Biology

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