Borna Disease Virus and the Brain

Abstract

Viruses with the ability to establish persistent infection in the central nervous system (CNS) can induce progressive neurologic disorders associated with diverse pathological manifestations. Clinical, epidemiological, and virological evidence supports the hypothesis that viruses contribute to human mental diseases whose etiology remains elusive. Therefore, the investigation of the mechanisms whereby viruses persist in the CNS and disturb normal brain function represents an area of research relevant to clinical and basic neurosciences. Borna disease virus (BDV) causes CNS disease in several vertebrate species characterized by behavioral abnormalities. Based on its unique features, BDV represents the prototype of a new virus family. BDV provides an important model for the investigation of the mechanisms and consequences of viral persistence in the CNS. The BDV paradigm is amenable to study virus-cell interactions in the CNS that can lead to neurodevelopmental abnormalities, immune-mediated damage, as well as alterations in cell differentiated functions that affect brain homeostasis. Moreover, seroepidemiological data and recent molecular studies indicate that BDV is associated with certain neuropsychiatric diseases. The potential role of BDV and of other yet to be uncovered BDV-related viruses in human mental health provides additional impetus for the investigation of this novel neurotropic infectious agent.

Identification of suitable reference genes for BDV-infected primary rat hippocampal neurons

“…It has been reported that BDV infects a range of animal species worldwide (3), including China (4,5). BDV infects neurons in the limbic system, and primarily in the hippocampus and the cortex, which has wide spread connections to diverse cortical areas (6). However, BDV infection is restricted to areas of the rat brain that are responsible for intensive neurodegeneration in newborn Sprague-Dawley rats, indicating that the function of immature neural cells is impaired by BDV (7).…”

Borna Disease Virus Requires Cholesterol in both Cellular Membrane and Viral Envelope for Efficient Cell Entry

“…Both host and viral factors contribute to a variable period of incubation and heterogeneity in the symptoms and pathology associated with BDV infection (14,16,29,42,44). BDV provides an important model for the investigation of both immune-mediated pathological events associated with virus-induced neurological disease and mechanisms whereby noncytolytic viruses induce neurodevelopmental and behavioral disturbances in the absence of inflammation (15,18,41). Moreover, serological data and molecular epidemiological studies suggest that BDV, or a BDV-like virus, can infect humans and that it might be associated with certain neuropsychiatric disorders (17,24), which further underscores the interest in understanding the mechanisms underlying BDV persistence in the CNS and its effect on brain cell functions.…”

A reverse genetics system for Borna disease virus

“…Moreover, serological data and molecular epidemiological studies indicate that BDV can infect humans and might be associated with certain neuropsychiatric disorders (Billich et al, 2002;Carbone, 2001;Planz et al, 2002;Richt et al, 1997;Richt & Rott, 2001;Rott & Becht, 1995; Staeheli et al, 2000). Both virus and host factors contribute to a variable period of incubation, as well as significant heterogeneity, in the symptoms and pathology associated with BDV infection (Gonzalez-Dunia et al, 1997;Hatalski et al, 1997;Ikuta et al, 2002;Richt et al, 1997;Rott & Becht, 1995; Staeheli et al, 2000).BDV is an enveloped virus with a non-segmented, negativestranded RNA genome. Its genome is about 8?9 kb long, the smallest among known negative-stranded RNA viruses, and has an organization similar to that of other mononegaviruses (de la Torre, 1994;Schneemann et al, 1995).…”