title: Neuropathogenesis of persistent infection with Borna disease virus.
abstract: Borna disease virus (BDV), belonging to the non-segmented, negative-stranded RNA viruses, persistently infects the central nervous system of many mammals. Neonatal BDV infection in rodent models induces neurodevelopmental disturbance without overt inflammatory responses, resulting in a wide range of neurobehavioral abnormalities, such as anxiety, abnormal play behaviors, and cognitive deficits, resembling those of autism patients. Therefore, studies of BDV could provide a valuable model to investigate neuropathogenesis of neurodevelopmental disorders. However, the detailed neuropathogenesis of BDV has not been revealed. Here, we proposed two novel mechanisms that may contribute to BDV neuropathology. The first mechanism is abnormal IGF signaling. Using transgenic mice expressing BDV P protein in glial cells (P-Tg) that show neurobehavioral abnormalities resembling those in BDV-infected animals, we found that the upregulation of insulin-like growth factor (IGF) binding protein 3 in the astrocytes disturbs the IGF signaling and induces the Purkinje cell loss in BDV infection. The other is the integration of BDV sequences into the host genome. We recently found that BDV mRNAs are reverse-transcribed and integrated into the genome of infected cells. BDV integrants have the potential to produce their translated products or piRNAs, suggesting that BDV might exhibit the pathogenicity thorough these molecules. We also demonstrated that BDV integrants affect neighboring gene expression. Collectively, BDV integrants may alter transcriptome of infected cells, affecting BDV neuropathology.
authors.affiliation: Department of Viral Oncology, Institute for Virus Research, Kyoto University.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Honda
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D001890:Borna Disease / Q000821:virology*; D001891:Borna disease virus / Q000472:pathogenicity*; D004195:Disease Models, Animal; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D065886:Neurodevelopmental Disorders / Q000821:virology*; D011689:Purkinje Cells / Q000473:pathology; D015398:Signal Transduction; D013002:Somatomedins; D059467:Transcriptome; D016662:Virus Integration
chemical_list: D018972:Insulin-Like Growth Factor Binding Protein 3; D013002:Somatomedins