RRC ID 61731
Author Nair SR, Abraham R, Sundaram S, Sreekumar E.
Title Interferon regulated gene (IRG) expression-signature in a mouse model of chikungunya virus neurovirulence.
Journal J Neurovirol
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.
Volume 23(6)
Pages 886-902
Published 2017-12-1
DOI 10.1007/s13365-017-0583-3
PII 10.1007/s13365-017-0583-3
PMID 29067635
MeSH Adaptor Proteins, Signal Transducing Animals Antigens / genetics Antigens / immunology Antigens, Differentiation, Myelomonocytic / genetics Antigens, Differentiation, Myelomonocytic / immunology Brain / immunology Brain / virology Carrier Proteins / genetics Carrier Proteins / immunology Cell Line Chikungunya Fever / genetics* Chikungunya Fever / immunology Chikungunya Fever / virology Chikungunya virus / immunology* Chikungunya virus / pathogenicity Cytoskeletal Proteins / genetics Cytoskeletal Proteins / immunology DEAD-box RNA Helicases / genetics DEAD-box RNA Helicases / immunology Disease Models, Animal Endopeptidases / genetics Endopeptidases / immunology Gene Expression Regulation Hepatocytes / immunology Hepatocytes / virology Host-Pathogen Interactions* Humans Immunity, Innate Interferon Regulatory Factors / genetics* Interferon Regulatory Factors / immunology Mice Mice, Inbred BALB C Microarray Analysis Neurons / immunology Neurons / virology RNA, Messenger / genetics* RNA, Messenger / immunology RNA-Binding Proteins Signal Transduction Transcription Factors / genetics Transcription Factors / immunology Transcriptome / immunology* Ubiquitin Thiolesterase Viral Proteins / genetics* Viral Proteins / immunology
IF 2.354
Human and Animal Cells HuH-7(RCB1366)