title: Depletion of Olig2 in oligodendrocyte progenitor cells infected by Theiler's murine encephalomyelitis virus.
abstract: Theiler's murine encephalomyelitis virus (TMEV) infects the central nervous system of mice and causes a demyelinating disease that is a model for multiple sclerosis. During the chronic phase of the disease, TMEV persists in oligodendrocytes and macrophages. Lack of remyelination has been attributed to insufficient proliferation and differentiation of oligodendrocyte progenitor cells (OPCs), but the molecular mechanisms remain unknown. Here, we employed pluripotent stem cell technologies to generate pure populations of mouse OPCs to study the temporal and molecular effects of TMEV infection. Global transcriptome analysis of RNA sequencing data revealed that TMEV infection of OPCs caused significant up-regulation of 1926 genes, whereas 1853 genes were significantly down-regulated compared to uninfected cells. Pathway analysis revealed that TMEV disrupted many genes required for OPC growth and maturation. Down-regulation of Olig2, a transcription factor necessary for OPC proliferation, was confirmed by real-time PCR, immunofluorescence microscopy, and western blot analysis. Depletion of Olig2 was not found to be specific to viral strain and did not require expression of the leader (L) protein, which is a multifunctional protein important for persistence, modulation of gene expression, and cell death. These data suggest that direct infection of OPCs by TMEV may inhibit remyelination during the chronic phase of TMEV-induced demyelinating disease.
authors.affiliation: Department of Biology, The University of Tampa, Tampa, FL, USA.
authors.forename: Bayleigh
authors.initials: B
authors.lastname: Benner
authors.affiliation: Department of Biology, The University of Tampa, Tampa, FL, USA.
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Martorell
authors.affiliation: Department of Biology, The University of Tampa, Tampa, FL, USA.
authors.forename: Padmanabhan
authors.initials: P
authors.lastname: Mahadevan
authors.affiliation: Department of Genetics and Genome Sciences, Case Western Reserve University School of Medicine, Cleveland, OH, USA.
authors.forename: Fadi J
authors.initials: FJ
authors.lastname: Najm
authors.affiliation: Department of Genetics and Genome Sciences, Case Western Reserve University School of Medicine, Cleveland, OH, USA.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Tesar
authors.affiliation: Department of Biology, The University of Tampa, Tampa, FL, USA. efreundt@ut.edu.
authors.forename: Eric C
authors.initials: EC
authors.lastname: Freundt
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D006224:Cricetinae; D003711:Demyelinating Diseases / Q000473:pathology / Q000821:virology*; D004847:Epithelial Cells / Q000821:virology; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D054884:Host-Pathogen Interactions; D051379:Mice; D058977:Molecular Sequence Annotation; D000073637:Oligodendrocyte Precursor Cells / Q000378:metabolism / Q000821:virology*; D000076104:Oligodendrocyte Transcription Factor 2 / Q000172:deficiency / Q000235:genetics*; D039904:Pluripotent Stem Cells / Q000378:metabolism / Q000821:virology*; D061251:Primary Cell Culture; D017945:Theilovirus / Q000235:genetics* / Q000378:metabolism; D059467:Transcriptome
chemical_list: C512773:Olig2 protein, mouse; D000076104:Oligodendrocyte Transcription Factor 2
keywords: Demyelination; Olig2; Oligodendrocyte progenitor cell; Theiler’s murine encephalomyelitis virus