title: Dynamic changes in global microRNAome and transcriptome reveal complex miRNA-mRNA regulated host response to Japanese Encephalitis Virus in microglial cells.
abstract: Microglia cells in the brain play essential role during Japanese Encephalitis Virus (JEV) infection and may lead to change in microRNA (miRNA) and mRNA profile. These changes may together control disease outcome. Using Affymetrix microarray platform, we profiled cellular miRNA and mRNA expression at multiple time points during viral infection in human microglial (CHME3) cells. In silico analysis of microarray data revealed a phased pattern of miRNAs expression, associated with JEV replication and provided unique signatures of infection. Target prediction and pathway enrichment analysis identified anti correlation between differentially expressed miRNA and the gene expression at multiple time point which ultimately affected diverse signaling pathways including Notch signaling pathways in microglia. Activation of Notch pathway during JEV infection was demonstrated in vitro and in vivo. The expression of a subset of miRNAs that target multiple genes in Notch signaling pathways were suppressed and their overexpression could affect JEV induced immune response. Further analysis provided evidence for the possible presence of cellular competing endogenous RNA (ceRNA) associated with innate immune response. Collectively, our data provide a uniquely comprehensive view of the changes in the host miRNAs induced by JEV during cellular infection and identify Notch pathway in modulating microglia mediated inflammation.
authors.affiliation: Vaccine and Infectious Disease Research Center, Translational Health Science and Technology Institute, Faridabad, India.
authors.forename: Bharti
authors.initials: B
authors.lastname: Kumari
authors.affiliation: Vaccine and Infectious Disease Research Center, Translational Health Science and Technology Institute, Faridabad, India.
authors.forename: Pratistha
authors.initials: P
authors.lastname: Jain
authors.affiliation: Computational Biology Group, Indian Association for the Cultivation of Science, Kolkata, India.
authors.forename: Shaoli
authors.initials: S
authors.lastname: Das
authors.affiliation: Computational Biology Group, Indian Association for the Cultivation of Science, Kolkata, India.
authors.forename: Suman
authors.initials: S
authors.lastname: Ghosal
authors.affiliation: National Brain Research Centre, Manesar, Haryana, India.
authors.forename: Bibhabasu
authors.initials: B
authors.lastname: Hazra
authors.affiliation: Innovative Life Discoveries Pvt. Ltd., Manesar, Haryana, India.
authors.forename: Ashish Chandra
authors.initials: AC
authors.lastname: Trivedi
authors.affiliation: National Brain Research Centre, Manesar, Haryana, India.
authors.forename: Anirban
authors.initials: A
authors.lastname: Basu
authors.affiliation: Computational Biology Group, Indian Association for the Cultivation of Science, Kolkata, India.
authors.forename: Jayprokas
authors.initials: J
authors.lastname: Chakrabarti
authors.affiliation: Vaccine and Infectious Disease Research Center, Translational Health Science and Technology Institute, Faridabad, India.
authors.forename: Sudhanshu
authors.initials: S
authors.lastname: Vrati
authors.affiliation: Vaccine and Infectious Disease Research Center, Translational Health Science and Technology Institute, Faridabad, India.
authors.forename: Arup
authors.initials: A
authors.lastname: Banerjee
mesh_terms: D000818:Animals; D002460:Cell Line; D003198:Computer Simulation; D004664:Encephalitis Virus, Japanese / Q000235:genetics*; D020869:Gene Expression Profiling / Q000379:methods*; D005786:Gene Expression Regulation; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D017628:Microglia / Q000166:cytology / Q000378:metabolism / Q000821:virology*; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D051880:Receptors, Notch / Q000235:genetics; D015398:Signal Transduction
chemical_list: D035683:MicroRNAs; D012333:RNA, Messenger; D051880:Receptors, Notch
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