Virus-Induced Transcriptional Changes in the Brain Include the Differential Expression of Genes Associated with Interferon, Apoptosis, Interleukin 17 Receptor A, and Glutamate Signaling as Well as Flavivirus-Specific Upregulation of tRNA Synthetases

ABSTRACT 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 b...

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Autores principales:	Penny Clarke, J. Smith Leser, Richard A. Bowen, Kenneth L. Tyler
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2014
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/9e205865d1544fbeb14883f5b4b3d726
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spelling	oai:doaj.org-article:9e205865d1544fbeb14883f5b4b3d7262021-11-15T15:45:13ZVirus-Induced Transcriptional Changes in the Brain Include the Differential Expression of Genes Associated with Interferon, Apoptosis, Interleukin 17 Receptor A, and Glutamate Signaling as Well as Flavivirus-Specific Upregulation of tRNA Synthetases10.1128/mBio.00902-142150-7511https://doaj.org/article/9e205865d1544fbeb14883f5b4b3d7262014-05-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00902-14https://doaj.org/toc/2150-7511ABSTRACT 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.Penny ClarkeJ. Smith LeserRichard A. BowenKenneth L. TylerAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 5, Iss 2 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Penny Clarke J. Smith Leser Richard A. Bowen Kenneth L. Tyler Virus-Induced Transcriptional Changes in the Brain Include the Differential Expression of Genes Associated with Interferon, Apoptosis, Interleukin 17 Receptor A, and Glutamate Signaling as Well as Flavivirus-Specific Upregulation of tRNA Synthetases
description	ABSTRACT 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.
format	article
author	Penny Clarke J. Smith Leser Richard A. Bowen Kenneth L. Tyler
author_facet	Penny Clarke J. Smith Leser Richard A. Bowen Kenneth L. Tyler
author_sort	Penny Clarke
title	Virus-Induced Transcriptional Changes in the Brain Include the Differential Expression of Genes Associated with Interferon, Apoptosis, Interleukin 17 Receptor A, and Glutamate Signaling as Well as Flavivirus-Specific Upregulation of tRNA Synthetases
title_short	Virus-Induced Transcriptional Changes in the Brain Include the Differential Expression of Genes Associated with Interferon, Apoptosis, Interleukin 17 Receptor A, and Glutamate Signaling as Well as Flavivirus-Specific Upregulation of tRNA Synthetases
title_full	Virus-Induced Transcriptional Changes in the Brain Include the Differential Expression of Genes Associated with Interferon, Apoptosis, Interleukin 17 Receptor A, and Glutamate Signaling as Well as Flavivirus-Specific Upregulation of tRNA Synthetases
title_fullStr	Virus-Induced Transcriptional Changes in the Brain Include the Differential Expression of Genes Associated with Interferon, Apoptosis, Interleukin 17 Receptor A, and Glutamate Signaling as Well as Flavivirus-Specific Upregulation of tRNA Synthetases
title_full_unstemmed	Virus-Induced Transcriptional Changes in the Brain Include the Differential Expression of Genes Associated with Interferon, Apoptosis, Interleukin 17 Receptor A, and Glutamate Signaling as Well as Flavivirus-Specific Upregulation of tRNA Synthetases
title_sort	virus-induced transcriptional changes in the brain include the differential expression of genes associated with interferon, apoptosis, interleukin 17 receptor a, and glutamate signaling as well as flavivirus-specific upregulation of trna synthetases
publisher	American Society for Microbiology
publishDate	2014
url	https://doaj.org/article/9e205865d1544fbeb14883f5b4b3d726
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Virus-Induced Transcriptional Changes in the Brain Include the Differential Expression of Genes Associated with Interferon, Apoptosis, Interleukin 17 Receptor A, and Glutamate Signaling as Well as Flavivirus-Specific Upregulation of tRNA Synthetases

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