title: The brain parenchyma has a type I interferon response that can limit virus spread.
abstract: The brain has a tightly regulated environment that protects neurons and limits inflammation, designated "immune privilege." However, there is not an absolute lack of an immune response. We tested the ability of the brain to initiate an innate immune response to a virus, which was directly injected into the brain parenchyma, and to determine whether this response could limit viral spread. We injected vesicular stomatitis virus (VSV), a transsynaptic tracer, or naturally occurring VSV-derived defective interfering particles (DIPs), into the caudate-putamen (CP) and scored for an innate immune response and inhibition of virus spread. We found that the brain parenchyma has a functional type I interferon (IFN) response that can limit VSV spread at both the inoculation site and among synaptically connected neurons. Furthermore, we characterized the response of microglia to VSV infection and found that infected microglia produced type I IFN and uninfected microglia induced an innate immune response following virus injection.
authors.affiliation: Department of Genetics, Harvard Medical School, Boston, MA 02115.|Department of Ophthalmology, Harvard Medical School, Boston, MA 02115.|Howard Hughes Medical Institute, Harvard Medical School, Boston, MA 02115.
authors.forename: Eugene
authors.initials: E
authors.lastname: Drokhlyansky
authors.affiliation: Department of Genetics, Harvard Medical School, Boston, MA 02115.|Department of Ophthalmology, Harvard Medical School, Boston, MA 02115.|Howard Hughes Medical Institute, Harvard Medical School, Boston, MA 02115.
authors.forename: Didem
authors.initials: D
authors.lastname: Göz Aytürk
authors.affiliation: Department of Microbiology and Immunobiology, Program in Virology, Harvard Medical School, Boston, MA 02115.
authors.forename: Timothy K
authors.initials: TK
authors.lastname: Soh
authors.affiliation: Department of Genetics, Harvard Medical School, Boston, MA 02115.|Department of Ophthalmology, Harvard Medical School, Boston, MA 02115.|Howard Hughes Medical Institute, Harvard Medical School, Boston, MA 02115.
authors.forename: Ryan
authors.initials: R
authors.lastname: Chrenek
authors.affiliation: Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115.
authors.forename: Elaine
authors.initials: E
authors.lastname: O'Loughlin
authors.affiliation: Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Madore
authors.affiliation: Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115.
authors.forename: Oleg
authors.initials: O
authors.lastname: Butovsky
authors.affiliation: Department of Genetics, Harvard Medical School, Boston, MA 02115; cepko@genetics.med.harvard.edu.|Department of Ophthalmology, Harvard Medical School, Boston, MA 02115.|Howard Hughes Medical Institute, Harvard Medical School, Boston, MA 02115.
authors.forename: Constance L
authors.initials: CL
authors.lastname: Cepko
mesh_terms: D000818:Animals; D001921:Brain / Q000276:immunology* / Q000821:virology; D007113:Immunity, Innate / Q000276:immunology*; D007370:Interferon Type I / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D000072356:Parenchymal Tissue / Q000276:immunology* / Q000821:virology; D054243:Vesicular Stomatitis / Q000276:immunology / Q000821:virology; D018116:Vesiculovirus / Q000254:growth & development / Q000276:immunology*; D014779:Virus Replication / Q000276:immunology
chemical_list: D007370:Interferon Type I
keywords: VSV; brain; innate immunity; interferon; vesicular stomatitis virus