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Journal of NeuroVirology
Published in: Journal of NeuroVirology 6/2017

01-12-2017

Interferon regulated gene (IRG) expression-signature in a mouse model of chikungunya virus neurovirulence

Authors: Sreeja R. Nair, Rachy Abraham, Sankar Sundaram, Easwaran Sreekumar

Published in: Journal of NeuroVirology | Issue 6/2017

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Abstract

Interferon regulated genes (IRGs) are critical in controlling virus infections. Here, we analyzed the expression profile of IRGs in the brain tissue in a mouse model of chikungunya virus (CHIKV) neurovirulence. Neurovirulence is one of the newer complications identified in disease caused by re-emerging strains of CHIKV, an alphavirus with positive-strand RNA in the Togaviridae family. In microarray analysis, we identified significant upregulation of 269 genes, out of which a predominant percentage (76%) was IRGs. The highly modulated IRGs included Ifit1, Ifi44, Ddx60, Usp18, Stat1, Rtp4, Mnda, Gbp3, Gbp4, Gbp7, Oasl2, Oas1g, Ly6a, Igtp, and Gbp10, along with many others exhibiting lesser changes in expression levels. We found that these IRG mRNA transcripts are modulated in parallel across CHIKV-infected mouse brain tissues, human neuronal cell line IMR-32 and hepatic cell line Huh-7. The genes identified to be highly modulated both in mouse brain and human neuronal cells were Ifit1, Ifi44, Ddx60, Usp18, and Mnda. In Huh-7 cells, however, only two IRGs (Gbp4 and Gbp7) showed a similar level of upregulation. Concordant modulation of IRGs in both mice and human cells indicates that they might play important roles in regulating CHIKV replication in the central nervous system (CNS). The induction of several IRGs in CNS during infection underscores the robustness of IRG-mediated innate immune response in CHIKV restriction. Further studies on these IRGs would help in evolving possibilities for their targeting in host-directed therapeutic interventions against CHIKV.
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Metadata
Title
Interferon regulated gene (IRG) expression-signature in a mouse model of chikungunya virus neurovirulence
Authors
Sreeja R. Nair
Rachy Abraham
Sankar Sundaram
Easwaran Sreekumar
Publication date
01-12-2017
Publisher
Springer International Publishing
Published in
Journal of NeuroVirology / Issue 6/2017
Print ISSN: 1355-0284
Electronic ISSN: 1538-2443
DOI
https://doi.org/10.1007/s13365-017-0583-3

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