title: T cell mediated suppression of neurotropic coronavirus replication in neural precursor cells.
abstract: Neural precursor cells (NPCs) are the subject of intense investigation for their potential to treat neurodegenerative disorders, yet the consequences of neuroinvasive virus infection of NPCs remain unclear. This study demonstrates that NPCs support replication following infection by the neurotropic JHM strain of mouse hepatitis virus (JHMV). JHMV infection leads to increased cell death and dampens IFN-γ-induced MHC class II expression. Importantly, cytokines secreted by CD4+ T cells inhibit JHMV replication in NPCs, and CD8+ T cells specifically target viral peptide-pulsed NPCs for lysis. Furthermore, treatment with IFN-γ inhibits JHMV replication in a dose-dependent manner. Together, these findings suggest that T cells play a critical role in controlling replication of a neurotropic virus in NPCs, a finding which has important implications when considering immune modulation for NPC-based therapies for treatment of human neurologic diseases.
authors.affiliation: Department of Molecular Biology & Biochemistry, University of California, Irvine 92697-3900, USA; Sue and Bill Gross Stem Cell Center, University of California, Irvine 92697-3900, USA.
authors.forename: Warren C
authors.initials: WC
authors.lastname: Plaisted
authors.affiliation: Department of Molecular Biology & Biochemistry, University of California, Irvine 92697-3900, USA; Sue and Bill Gross Stem Cell Center, University of California, Irvine 92697-3900, USA.
authors.forename: Jason G
authors.initials: JG
authors.lastname: Weinger
authors.affiliation: Department of Molecular Biology & Biochemistry, University of California, Irvine 92697-3900, USA; Sue and Bill Gross Stem Cell Center, University of California, Irvine 92697-3900, USA; Multiple Sclerosis Research Center, University of California, Irvine 92697-3900, USA; Institute for Immunology, University of California, Irvine 92697-3900, USA.
authors.forename: Craig M
authors.initials: CM
authors.lastname: Walsh
authors.affiliation: Department of Molecular Biology & Biochemistry, University of California, Irvine 92697-3900, USA; Sue and Bill Gross Stem Cell Center, University of California, Irvine 92697-3900, USA; Multiple Sclerosis Research Center, University of California, Irvine 92697-3900, USA; Institute for Immunology, University of California, Irvine 92697-3900, USA. Electronic address: tom.lane@path.utah.edu.
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Lane
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D018352:Coronavirus Infections / Q000276:immunology / Q000662:veterinary* / Q000821:virology; D051379:Mice; D008810:Mice, Inbred C57BL; D006517:Murine hepatitis virus / Q000235:genetics / Q000502:physiology*; D058953:Neural Stem Cells / Q000276:immunology / Q000821:virology*; D012376:Rodent Diseases / Q000276:immunology / Q000821:virology*; D056189:Viral Tropism; D014779:Virus Replication
keywords: Host response; Neural precursor cells; T cells; Virus