title: The pathogenesis of bornaviral diseases in mammals.
abstract: Natural bornavirus infections and their resulting diseases are largely restricted to horses and sheep in Central Europe. The disease also occurs naturally in cats, and can be induced experimentally in laboratory rodents and numerous other mammals. Borna disease virus-1 (BoDV-1), the cause of most cases of mammalian Borna disease, is a negative-stranded RNA virus that replicates within the nucleus of target cells. It causes severe, often lethal, encephalitis in susceptible species. Recent events, especially the discovery of numerous new species of bornaviruses in birds and a report of an acute, lethal bornaviral encephalitis in humans, apparently acquired from squirrels, have revived interest in this remarkable family of viruses. The clinical manifestations of the bornaviral diseases are highly variable. Thus, in addition to acute lethal encephalitis, they can cause persistent neurologic disease associated with diverse behavioral changes. They also cause a severe retinitis resulting in blindness. In this review, we discuss both the pathological lesions observed in mammalian bornaviral disease and the complex pathogenesis of the neurologic disease. Thus infected neurons may be destroyed by T-cell-mediated cytotoxicity. They may die as a result of excessive inflammatory cytokine release from microglia. They may also die as a result of a 'glutaminergic storm' due to a failure of infected astrocytes to regulate brain glutamate levels.
authors.affiliation: Department of Veterinary Pathobiology and the Schubot Exotic Bird Health Center,Texas A&M University,College of Veterinary Medicine and Biomedical Sciences,College Station,Texas 77843,USA.
authors.forename: Ian
authors.identifier: 0000-0001-5311-2581
authors.initials: I
authors.lastname: Tizard
authors.affiliation: Department of Veterinary Pathobiology and the Schubot Exotic Bird Health Center,Texas A&M University,College of Veterinary Medicine and Biomedical Sciences,College Station,Texas 77843,USA.
authors.forename: Judith
authors.initials: J
authors.lastname: Ball
authors.affiliation: Department of Veterinary Pathobiology and the Schubot Exotic Bird Health Center,Texas A&M University,College of Veterinary Medicine and Biomedical Sciences,College Station,Texas 77843,USA.
authors.forename: George
authors.initials: G
authors.lastname: Stoica
authors.affiliation: Department of Veterinary Pathobiology and the Schubot Exotic Bird Health Center,Texas A&M University,College of Veterinary Medicine and Biomedical Sciences,College Station,Texas 77843,USA.
authors.forename: Susan
authors.initials: S
authors.lastname: Payne
mesh_terms: D000818:Animals; D001890:Borna Disease / Q000453:epidemiology / Q000473:pathology* / Q000821:virology; D001891:Borna disease virus; D005060:Europe / Q000453:epidemiology; D006801:Humans; D008322:Mammals
keywords: Bornavirus; astrocytes; encephalitis; excitotoxicity; glutamate; mammals; microglial activation