Borna Disease Virus Infection of Adult and Neonatal Rats: Models for Neuropsychiatric Disease

Hornig, Mady; Solbrig, Marylou V.; Horscroft, Nigel; Weißenböck, H.; Lipkin, W. Ian

doi:10.1007/978-3-662-10356-2_8

Cited by 56 publications

(73 citation statements)

References 75 publications

(68 reference statements)

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“…However, it is also true that there are significant differences between persistently BDV-infected rodents and P transgenic mice in the behavioral and neurochemical alterations. In neonatally infected rats, BDV causes significant neuroanatomical disturbances characterized by degeneration of the dentate gyrus, cortical shrinkage, and cerebellar hypoplasia (13). It has been also demonstrated that neonatally infected rats show abnormal social play behavior, but not aggressive behavior, by the intruder-resident paradigm (12).…”

Section: Discussionmentioning

confidence: 99%

“…Natural infection of BDV has now been found in a wide variety of vertebrates, suggesting that the host range of this virus probably includes all warm-blooded animals (9,10). BDV persistently infects the CNS of many animal species and causes behavioral disturbances, such as anxiety, aggression, hyperactivity, abnormal play behavior, and cognitive deficits, reminiscent of autism, schizophrenia, and mood disorders (11)(12)(13)(14). Thus, studies on this virus provide an important paradigm for the investigation of the mechanisms by which virus infection induces neurobehavioral disorders.…”

mentioning

confidence: 99%

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Glial expression of Borna disease virus phosphoprotein induces behavioral and neurological abnormalities in transgenic mice

Kamitani

Ono

Yoshino

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

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One hypothesis for the etiology of behavioral disorders is that infection by a virus induces neuronal cell dysfunctions resulting in a wide range of behavioral abnormalities. However, a direct linkage between viral infections and neurobehavioral disturbances associated with human psychiatric disorders has not been identified. Here, we show that transgenic mice expressing the phosphoprotein (P) of Borna disease virus (BDV) in glial cells develop behavioral abnormalities, such as enhanced intermale aggressiveness, hyperactivity, and spatial reference memory deficit. We demonstrate that the transgenic brains exhibit a significant reduction in brain-derived neurotrophic factor and serotonin receptor expression, as well as a marked decrease in synaptic density. These results demonstrate that glial expression of BDV P leads to behavioral and neurobiological disturbances resembling those in BDVinfected animals. Furthermore, the lack of reactive astrocytosis and neuronal degeneration in the brains indicates that P can directly induce glial cell dysfunction and also suggests that the transgenic mice may exhibit neuropathological and neurophysiological abnormalities resembling those of psychiatric patients. Our results provide a new insight to explore the relationship between viral infections and neurobehavioral disorders. N eurobehavioral disorder is a complex disease that must arise from the actions of many genes and͞or environmental factors. A number of working hypotheses propose that viral infection, as an environmental factor, contributes to the induction of neuropathological and neurophysiological disturbances, resulting in a wide range of behavioral abnormalities (1-3). Studies using animal models reveal that viruses can induce neurobehavioral disturbances predominantly through an indirect pathway that involves the release of various factors by infiltrating cells or by glial cells (3-5). This process seems to be a common pathway to neuronal injury in a wide variety of neurodegenerative disorders in which glial proliferation typically accompanies. In the case of major psychiatric disorders, however, a spectrum of neurological abnormalities associated with glial cell dysfunction is found in brains without neuronal degeneration (2, 6-8). Despite increased insight into the mechanisms of the neuropathogenesis of different viruses, viral infections or specific antigens that develop neurobehavioral abnormalities associated with psychiatric disorders have not yet been identified.Borna disease virus (BDV) is a highly neurotropic virus that belongs to the Mononegavirales. Natural infection of BDV has now been found in a wide variety of vertebrates, suggesting that the host range of this virus probably includes all warm-blooded animals (9, 10). BDV persistently infects the CNS of many animal species and causes behavioral disturbances, such as anxiety, aggression, hyperactivity, abnormal play behavior, and cognitive deficits, reminiscent of autism, schizophrenia, and mood disorders (11)(12)(13)(14). Thus, studies on this virus...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Glial expression of Borna disease virus phosphoprotein induces behavioral and neurological abnormalities in transgenic mice

Kamitani

Ono

Yoshino

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

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“…Although Borna disease virus (BDV) is a prototypical mammalian bornavirus that causes neurobehavioral disorders in rodents (1), the association between BDV and human psychiatric disorders remains controversial (2). Recently, bornaviruses related to BDV were discovered in birds (i.e., avian bornaviruses) (3).…”

Section: Communicated By Masayuki Saijomentioning

confidence: 99%

Detection of Antibodies against Borna Disease Virus Proteins in an Autistic Child and Her Mother

et al. 2017

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“…Although it has also been suggested that BDV may infect humans and might be associated with certain neuropsychiatric disorders (2), this idea is highly controversial (5). Nonetheless, experimental infection with BDV serves as an important model system for the investigation of viral persistence in the central nervous system and its associated disorders (1,2,6).…”

mentioning

confidence: 99%

Crystal structure of the Borna disease virus matrix protein (BDV-M) reveals ssRNA binding properties

Neumann¹,

Lieber²,

Meyer³

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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Borna Disease Virus Infection of Adult and Neonatal Rats: Models for Neuropsychiatric Disease

Cited by 56 publications

References 75 publications

Glial expression of Borna disease virus phosphoprotein induces behavioral and neurological abnormalities in transgenic mice

Glial expression of Borna disease virus phosphoprotein induces behavioral and neurological abnormalities in transgenic mice

Detection of Antibodies against Borna Disease Virus Proteins in an Autistic Child and Her Mother

Crystal structure of the Borna disease virus matrix protein (BDV-M) reveals ssRNA binding properties

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