Gene expression in the brain during reovirus encephalitis

• Published in: Journal of neurovirology 2010-02, Vol.16 (1), p.56-71
• Main Authors: Tyler, Kenneth L, Leser, J Smith, Phang, Tzu L, Clarke, Penny
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis - genetics; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Brain - metabolism; Caspases, Effector - metabolism; Cell Line; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Disease Progression; Encephalitis, Viral - etiology; Encephalitis, Viral - metabolism; Encephalitis, Viral - pathology; Gene Expression Profiling; Gene Expression Regulation; Human viral diseases; Humans; Immunity, Innate - genetics; Immunology; Infectious Diseases; Interferon Regulatory Factors - metabolism; Interferons - biosynthesis; Interferons - genetics; Medical sciences; Mice; Neurology; Neurosciences; NF-kappa B - metabolism; Promoter Regions, Genetic; Reoviridae; Reoviridae Infections - complications; Reoviridae Infections - metabolism; Reoviridae Infections - virology; Signal Transduction - genetics; STAT1 Transcription Factor - metabolism; Viral diseases; Viral diseases of the nervous system; Virology
• ISSN: 1355-0284; 1538-2443
• DOI: 10.3109/13550280903586394

Viral encephalitis remains a significant cause of morbidity and mortality throughout the world. We performed microarray analysis to identify genes and pathways that are differentially regulated during reovirus encephalitis and that may provide novel therapeutic targets for virus-induced diseases of the central nervous system (CNS). An increase in the expression of 130 cellular genes was found in the brains of reovirus-infected mice at early times post infection, compared to mock-infected controls. The up-regulation of these genes was consistent with activation of innate immune responses, particularly interferon signaling. At later times post infection, when significant CNS injury is present and mice exhibit signs of severe neurologic disease, many more (1374) genes were up-regulated, indicating that increased gene expression correlates with disease pathology. Virus-induced gene expression at late times post infection was again consistent with the activation of innate immune responses. However, additional significant pathways included those associated with cytokine signaling and apoptosis, both of which can contribute to CNS injury. This is the first report comparing virus-induced cellular gene and pathway regulation at early and late times following virus infection of the brain. The shift of virus-induced gene expression from innate immune responses at early times post infection to cytokine signaling and apoptosis at later times suggests a potential therapeutic strategy that preserves early protective responses whilst inhibiting later responses that contribute to pathogenesis.