title: Intrinsic responses to Borna disease virus infection of the central nervous system.
abstract: Immune cells invading the central nervous system (CNS) in response to Borna disease virus (BDV) antigens are central to the pathogenesis of Borna disease (BD). We speculate that the response of the resident cells of the brain to infection may be involved in the sensitization and recruitment of these inflammatory cells. To separate the responses of resident cells from those of cells infiltrating from the periphery, we used dexamethasone to inhibit inflammatory reactions in BD. Treatment with dexamethasone prevented the development of clinical signs of BD, and the brains of treated animals showed no neuropathological lesions and a virtual absence of markers of inflammation, cell infiltration, or activation normally seen in the CNS of BDV-infected rats. In contrast, treatment with dexamethasone exacerbated the expression of BDV RNA, which was paralleled by a similarly elevated expression of mRNAs for egr-1, c-fos, and c-jun. Furthermore, dexamethasone failed to inhibit the increase in expression of mRNAs for tumor necrosis factor alpha, macrophage inflammatory protein 1 beta, interleukin 6, and mob-1, which occurs in the CNS of animals infected with BDV. Our findings suggest that these genes, encoding transcription factors, chemokines, and proinflammatory cytokines, might be directly activated in CNS resident cells by BDV. This result supports the hypothesis that the initial phase of the inflammatory response to BDV infection in the brain may be dependent upon virus-induced activation of CNS resident cells.
authors.affiliation: Department of Microbiology and Immunology, Thomas Jefferson University, Philadelphia, PA 19107-6799, USA.
authors.forename: K
authors.initials: K
authors.lastname: Morimoto
authors.forename: D C
authors.initials: DC
authors.lastname: Hooper
authors.forename: A
authors.initials: A
authors.lastname: Bornhorst
authors.forename: S
authors.initials: S
authors.lastname: Corisdeo
authors.forename: M
authors.initials: M
authors.lastname: Bette
authors.forename: Z F
authors.initials: ZF
authors.lastname: Fu
authors.forename: M K
authors.initials: MK
authors.lastname: Schäfer
authors.forename: H
authors.initials: H
authors.lastname: Koprowski
authors.forename: E
authors.initials: E
authors.lastname: Weihe
authors.forename: B
authors.initials: B
authors.lastname: Dietzschold
mesh_terms: D000818:Animals; D001483:Base Sequence; D001890:Borna Disease / Q000276:immunology / Q000503:physiopathology*; D001891:Borna disease virus / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D002493:Central Nervous System Diseases / Q000276:immunology / Q000503:physiopathology* / Q000821:virology*; D054407:Chemokine CCL4; D054357:Chemokine CXCL10; D019743:Chemokines, CXC; D016207:Cytokines / Q000096:biosynthesis*; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000096:biosynthesis; D003907:Dexamethasone / Q000494:pharmacology*; D051766:Early Growth Response Protein 1; D005260:Female; D016762:Genes, fos; D016758:Genes, jun; D017874:Immediate-Early Proteins; D007150:Immunohistochemistry; D007249:Inflammation / Q000517:prevention & control; D007371:Interferon-gamma / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D019402:Macrophage Inflammatory Proteins / Q000096:biosynthesis; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000096:biosynthesis; D012367:RNA, Viral / Q000096:biosynthesis*; D051381:Rats; D011917:Rats, Inbred Lew; D014157:Transcription Factors / Q000096:biosynthesis; D014158:Transcription, Genetic / Q000187:drug effects*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: C114753:CXCL10 protein, human; D054407:Chemokine CCL4; D054357:Chemokine CXCL10; D019743:Chemokines, CXC; C091326:Cxcl10 protein, rat; D016207:Cytokines; D017931:DNA Primers; D004268:DNA-Binding Proteins; D051766:Early Growth Response Protein 1; C486110:Egr1 protein, rat; D017874:Immediate-Early Proteins; D015850:Interleukin-6; D019402:Macrophage Inflammatory Proteins; D012333:RNA, Messenger; D012367:RNA, Viral; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha; D003907:Dexamethasone; D007371:Interferon-gamma