title: Distinct neural stem cell tropism, early immune activation, and choroid plexus pathology following coxsackievirus infection in the neonatal central nervous system.
abstract: Coxsackievirus B3 (CVB3) and lymphocytic choriomeningitis virus (LCMV) are both neurotropic RNA viruses, which can establish a persistent infection and cause meningitis and encephalitis in the neonatal host. Utilizing our neonatal mouse model of infection, we evaluated the consequences of early viral infection upon the host central nervous system (CNS) by comparing CVB3 and LCMV infection. Both viruses expressed high levels of viral protein in the choroid plexus and subventricular zone (SVZ), a region of neurogenesis. LCMV infected a greater number of cells in the SVZ and targeted both nestin(+) (neural progenitor cell marker) and olig2(+) (glial progenitor marker) cells at a relatively equal proportion. In contrast, CVB3 preferentially infected nestin(+) cells within the SVZ. Microarray analysis revealed differential kinetics and unique host gene expression changes for each infection. MHC class I gene expression, several developmental-related Hox genes, and transthyretin (TTR), a protein secreted in the cerebrospinal fluid by the choroid plexus, were specifically downregulated following CVB3 infection. Also, we identified severe pathology in the choroid plexus of CVB3-infected animals at 48 h post infection accompanied by a decrease in the level of TTR and carbonic anhydrase II. These results demonstrate broader neural progenitor and stem cell (NPSC) tropism for LCMV in the neonatal CNS, whereas CVB3 targeted a more specific subset of NPSCs, stimulated a distinct early immune response, and induced significant acute damage in the choroid plexus.
authors.affiliation: The Integrated Regenerative Research Institute (IRRI) at San Diego State University, Cell & Molecular Biology Joint Doctoral Program, Department of Biology, San Diego State University, San Diego, CA, USA.
authors.forename: Jenna M
authors.initials: JM
authors.lastname: Puccini
authors.affiliation: The Integrated Regenerative Research Institute (IRRI) at San Diego State University, Cell & Molecular Biology Joint Doctoral Program, Department of Biology, San Diego State University, San Diego, CA, USA.
authors.forename: Chelsea M
authors.initials: CM
authors.lastname: Ruller
authors.affiliation: The Integrated Regenerative Research Institute (IRRI) at San Diego State University, Cell & Molecular Biology Joint Doctoral Program, Department of Biology, San Diego State University, San Diego, CA, USA.
authors.forename: Scott M
authors.initials: SM
authors.lastname: Robinson
authors.affiliation: Department of Molecular Biology and Biochemistry, UC Irvine, Irvine, CA, USA.
authors.forename: Kristeene A
authors.initials: KA
authors.lastname: Knopp
authors.affiliation: Department of Molecular Biology and Biochemistry, UC Irvine, Irvine, CA, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Buchmeier
authors.affiliation: Department of Biology and Center for Microbial Sciences, San Diego State University, San Diego, CA, USA.
authors.forename: Kelly S
authors.initials: KS
authors.lastname: Doran
authors.affiliation: The Integrated Regenerative Research Institute (IRRI) at San Diego State University, Cell & Molecular Biology Joint Doctoral Program, Department of Biology, San Diego State University, San Diego, CA, USA.
authors.forename: Ralph
authors.initials: R
authors.lastname: Feuer
mesh_terms: D000818:Animals; D024402:Carbonic Anhydrase II / Q000378:metabolism; D002490:Central Nervous System / Q000821:virology*; D002831:Choroid Plexus / Q000378:metabolism / Q000473:pathology*; D003384:Coxsackievirus Infections / Q000276:immunology* / Q000473:pathology; D004195:Disease Models, Animal; D005455:Fluorescent Antibody Technique; D005786:Gene Expression Regulation / Q000235:genetics / Q000502:physiology*; D008216:Lymphocytic Choriomeningitis / Q000276:immunology* / Q000473:pathology; D051379:Mice; D046228:Microarray Analysis; D064231:Nestin / Q000378:metabolism; D058953:Neural Stem Cells / Q000502:physiology* / Q000821:virology
chemical_list: D064231:Nestin; D024402:Carbonic Anhydrase II