title: Induction of Multiple miR-200/182 Members in the Brains of Mice Are Associated with Acute Herpes Simplex Virus 1 Encephalitis.
abstract: Important roles of microRNAs (miRNAs) in regulating the host response during viral infection have begun to be defined. However, little is known about the functional roles of miRNAs within an in vivo acute viral encephalitis model. We therefore identified global changes in miRNA expression during acute herpes simplex virus type 1 (HSV-1) encephalitis (HSVE) in mice. We found that many of the highly upregulated miRNAs (miR-155, miR-146a and miR-15b) detected in HSV-1 infected brain tissue are known regulators of inflammation and innate immunity. We also observed upregulation of 7 members belonging to the related group of miRNAs, the miR-200 family and miR-182 cluster (miR-200/182). Using in situ hybridization, we found that these miRNAs co-localized to regions of the brain with severe HSVE-related pathology and were upregulated in various cell types including neurons. Induction was apparent but not limited to cells in which HSV-1 was detected by immunohistochemistry, suggesting possible roles of these miRNAs in the host response to viral-induced tissue damage. Bioinformatic prediction combined with gene expression profiling revealed that the induced miR-200/182 members could regulate the biosynthesis of heparan sulfate proteoglycans. Using luciferase assays, we found that miR-96, miR-141, miR-183 and miR-200c all potentially targeted the syndecan-2 gene (Sdc2), which codes for a cell surface heparan sulfate proteoglycan involved in HSV-1 cellular attachment and entry.
authors.affiliation: Department of Medical Microbiology and Infectious Diseases, College of Medicine, Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada.|Molecular PathoBiology, National Microbiology Laboratory, Canadian Science Centre for Human and Animal Health, Public Health Agency of Canada, Winnipeg, Manitoba, Canada.
authors.forename: Anna
authors.initials: A
authors.lastname: Majer
authors.affiliation: Department of Medical Microbiology and Infectious Diseases, College of Medicine, Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada.|Molecular PathoBiology, National Microbiology Laboratory, Canadian Science Centre for Human and Animal Health, Public Health Agency of Canada, Winnipeg, Manitoba, Canada.
authors.forename: Kyle A
authors.initials: KA
authors.lastname: Caligiuri
authors.affiliation: Molecular PathoBiology, National Microbiology Laboratory, Canadian Science Centre for Human and Animal Health, Public Health Agency of Canada, Winnipeg, Manitoba, Canada.
authors.forename: Kamilla K
authors.initials: KK
authors.lastname: Gale
authors.affiliation: Molecular PathoBiology, National Microbiology Laboratory, Canadian Science Centre for Human and Animal Health, Public Health Agency of Canada, Winnipeg, Manitoba, Canada.
authors.forename: Yulian
authors.initials: Y
authors.lastname: Niu
authors.affiliation: Molecular PathoBiology, National Microbiology Laboratory, Canadian Science Centre for Human and Animal Health, Public Health Agency of Canada, Winnipeg, Manitoba, Canada.
authors.forename: Clark S
authors.initials: CS
authors.lastname: Phillipson
authors.affiliation: Department of Medical Microbiology and Infectious Diseases, College of Medicine, Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada.|Viral Diseases, National Microbiology Laboratory, Canadian Science Centre for Human and Animal Health, Public Health Agency of Canada, Winnipeg, Manitoba, Canada.
authors.forename: Timothy F
authors.initials: TF
authors.lastname: Booth
authors.affiliation: Department of Medical Microbiology and Infectious Diseases, College of Medicine, Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada.|Molecular PathoBiology, National Microbiology Laboratory, Canadian Science Centre for Human and Animal Health, Public Health Agency of Canada, Winnipeg, Manitoba, Canada.
authors.forename: Stephanie A
authors.identifier: http://orcid.org/0000-0001-8108-5955
authors.initials: SA
authors.lastname: Booth
mesh_terms: D000208:Acute Disease; D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000821:virology; D002522:Chlorocebus aethiops; D019295:Computational Biology; D020803:Encephalitis, Herpes Simplex / Q000235:genetics* / Q000821:virology; D005260:Female; D020869:Gene Expression Profiling; D015967:Gene Expression Regulation, Viral; D019812:Heparan Sulfate Proteoglycans / Q000378:metabolism; D018259:Herpesvirus 1, Human / Q000235:genetics; D007113:Immunity, Innate; D007249:Inflammation; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D053669:Syndecan-2 / Q000235:genetics*; D059467:Transcriptome; D015854:Up-Regulation; D014709:Vero Cells
chemical_list: D019812:Heparan Sulfate Proteoglycans; D035683:MicroRNAs; C543718:Mirn141 microRNA, mouse; C540524:Mirn182 microRNA, mouse; C543802:Mirn183 microRNA, mouse; C543719:Mirn200 microRNA, mouse; C541554:Mirn96 microRNA, mouse; C508246:Sdc2 protein, mouse; D053669:Syndecan-2