Flaviviruses, particularly Japanese encephalitis virus (JEV) and West Nile virus (WNV), are important causes of virus-induced central nervous system (
CNS) disease in humans. We used microarray analysis to identify cellular genes that are differentially regulated following
infection of the brain with JEV (P3) or WNV (New York 99). Gene expression data for these flaviviruses were compared to those obtained following
infection of the brain with reovirus (type 3 Dearing), an unrelated neurotropic virus. We found that a large number of genes were up-regulated by all three viruses (using the criteria of a change of >2-fold and a P value of <0.001), including genes associated with
interferon signaling, the immune system,
inflammation, and cell death/survival signaling. In addition, genes associated with
glutamate signaling were down-regulated in
infections with all three viruses (criteria, a >2-fold change and a P value of <0.001). These genes may serve as broad-spectrum therapeutic targets for virus-induced
CNS disease. A distinct set of genes were up-regulated following
flavivirus infection but not following
infection with reovirus. These genes were associated with tRNA charging and may serve as therapeutic targets for flavivirus-induced
CNS disease. IMPORTANCE
Viral infections of the central nervous system (CNS) are an important cause of morbidity and mortality. Treatment options for virus-induced
CNS disease are limited, and for many clinically important neurotropic viruses, no specific
therapy of proven benefit is currently available. We performed microarray analysis to identify genes that are differentially regulated in the brain following
virus infection in order to identify pathways that might provide novel therapeutic targets for virus-induced
CNS disease. Although several studies have described gene expression changes following
virus infection of the brain, this report is the first to directly compare large-scale gene expression data from different viruses. We identified genes that are differentially regulated in
infection of the brain with viruses from different families and those which appear to be specific to
flavivirus infections.