Borna virus replicated persistently in the brains of rats, causing frenzied and apathetic behavioral states in sequence but no mortality. The transient frenzied behavior was caused by an immune-mediated, cytolytic, encephalitic response that was unexpectedly self-limiting. Cessation of active pathological processes coincided with the onset of the passive phase of the disease. This study thus demonstrates suppression of virus-specific inflammation despite continuous viral replication and describes a new mechanism by which chronic encephalitis may become established.

Borna disease virus causes a rare meningoencephalitis in horses and sheep and has been shown to produce behavioral effects in some species. The possibility that the Borna virus is associated with mental disorders in humans was evaluated by examining serum samples from 979 psychiatric patients and 200 normal volunteers for the presence of Borna virus-specific antibodies. Antibodies were detected by the indirect immunofluorescence focus assay. Antibodies to the virus were demonstrated in 16 of the patients but none of the normal volunteers. The patients with the positive serum samples were characterized by having histories of affective disorders, particularly of a cyclic nature. Further studies are needed to define the possible involvement of Borna virus in human psychiatric disturbances.

Borna disease virus is an unclassified agent that causes a rare but fatal encephalitis in horses in Germany. In experimental animals the virus causes acute fatal encephalitis in some instances and chronic encephalitis with abnormal behavior in others. In initial studies of the pathogenesis of the latter disease in rats, the virus was shown to replicate only in the nervous system, with the greatest concentration of infectivity in the cerebrum and eyes. Viral replication continued indefinitely in both newborn and adult rats. The adult animals developed self-limiting, necrotizing encephalitis in the cerebrum, with inflammation spreading to the retina. Inflammation receded after two months, however, with concomitant cessation of necrosis; static hydrocephalus was observed at this point. Levels of viral replication were unaffected by these changes. Rats became frenzied and aggressive during the encephalitic period but became permanently passive and inactive after inflammation receded. Infected neonates and immunosuppressed adults did not become ill. The frenzied behavior and subsequent blindness in immunocompetent adults were therefore attributed to a uniquely transient immunopathologic reaction targeted to centers in the limbic system and retinal neurons.

Borna disease (BD) virus from infected brain tissue of horses or rabbits could be grown in embryonic brain cells from rabbits or rats with high virus yields. The cells became persistently infected and could be subcultivated without loss of infectivity. Cocultivation of infected rabbit brain (ERB) cells with GMK-, Vero-, or MDCK-cells led to persistently infected cell lines. BD virus grown in MDCK cells after cocultivation became adapted to this cell type and could be used directly for further infection of MDCK cells.

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Inoculation induced persistent infection, clinical signs, and seroconversion.

The aim of this study was to gain more detailed insights into the genetic evolution and variability of Borna disease virus (BDV). Phylogenetic analyses were performed on field viruses originating from naturally infected animals, the BDV vaccine strain ‘Dessau’, four widely used laboratory strains and the novel BDV subtype No/98. Four regions of the BDV genome were analysed: the complete p40, p10 and p24 genes and the 5′-untranslated region of the X/P transcript. BDV isolates from the same geographical area exhibited a clearly higher degree of identity to each other than to BDV isolates from other regions, independent of host species and year of isolation. Five different clusters could be established within endemic areas, corresponding to the geographical regions from which the viruses originated: (i) a Swiss, Austrian and Liechtenstein Rhine valley group, related closely to the geographically bordering Baden-Wurttemberg and Bavaria II group (ii) in the western part of Germany; (iii) a third group, called Bavaria I group, limited in occurrence to Bavaria; (iv) a southern Saxony-Anhalt and bordering northern Saxony group, bound to the territories of these federal states in the eastern part of Germany; and (v) a mixed group, consisting of samples from different areas of Germany; however, these were mainly from the federal states of Thuringia and Lower Saxony. The laboratory strains and the vaccine strain clustered within these groups according to their geographical origins. All field and laboratory strains, as well as the vaccine strain, clearly segregated from the recently described and highly divergent BDV strain No/98, which originated from an area in Austria where Borna disease is not endemic.

In this study it has been shown that infection of mother rats by Borna disease virus (BDV) from infected newborns led to a fatal disease. This differed both in clinical symptoms and in histological alterations from the form of the disease which occurred after intracerebral (i.c.) infection. Both parameters were, however, similar to those seen after experimental intranasal (i.n.) infection of adult rats. Detailed immunohistological studies showed clearly that after experimental i.n. infection, the infecting virus migrates intraaxonally from the neuroreceptors in the olfactory epithelium into the brain. It is therefore suggested that i.n. transmission is an important route of natural BDV infection.