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Novel Strategy for Treatment of Viral Central Nervous System Infection by Using a Cell-Permeating Inhibitor of c-Jun N-Terminal Kinaseâ–¿
- Source :
- Journal of Virology
- Publication Year :
- 2007
- Publisher :
- American Society for Microbiology, 2007.
-
Abstract
- Viral encephalitis is a major cause of morbidity and mortality worldwide, yet there is no proven efficacious therapy for most viral infections of the central nervous system (CNS). Many of the viruses that cause encephalitis induce apoptosis and activate c-Jun N-terminal kinase (JNK) following infection. We have previously shown that reovirus infection of epithelial cell lines activates JNK-dependent apoptosis. We now show that reovirus infection resulted in activation of JNK and caspase-3 in the CNS. Treatment of reovirus-infected mice with a cell-permeating peptide that competitively inhibits JNK activity resulted in significantly prolonged survival of intracerebrally infected mice following an otherwise lethal challenge with T3D (100× 50% lethal dose). Protection correlated with reduced CNS injury, reduced neuronal apoptosis, and reduced c-Jun activation without altering the viral titer or viral antigen distribution. Given the efficacy of the inhibitor in protecting mice from viral encephalitis, JNK inhibition represents a promising and novel treatment strategy for viral encephalitis.
- Subjects :
- Central Nervous System
viruses
Immunology
Caspase 3
Apoptosis
Biology
Microbiology
Cell Line
Mice
Virology
Vaccines and Antiviral Agents
medicine
Animals
Humans
Encephalitis, Viral
Enzyme Inhibitors
Mammalian orthoreovirus 3
Neurons
Kinase
Viral encephalitis
c-jun
Lethal dose
JNK Mitogen-Activated Protein Kinases
medicine.disease
Reoviridae Infections
Cell culture
Insect Science
Peptides
Encephalitis
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Journal of Virology
- Accession number :
- edsair.doi.dedup.....3e240048f3a31584deb4456a55e03ef6