Abstract

Borna disease virus (BDV) is an RNA-virus persistently infecting the central nervous system of, and thereby causing neurological disorders in, several animal species, possibly including humans. Although several aspects of BDV and its pathologies have been studied for more than 100 years, further elucidation of the epidemiology and pathogenesis, and the development of reliable detection methods,is needed. This thesis describes the relationship between BDV and its hosts, with special emphasis on virus-host interactions and virus detection. The aims were to improve current detection methods, and to increase the knowledge of virus-host interactions, especially in naturally infected animals. First, a real-time RT-PCR assay for BDV detection was developed; and second this method, as well as serology, was evaluated for use when diagnosing Borna disease (BD) in cats. These studies suggest that serology is the most useful tool to further strengthen a clinical suspicion of feline BD, whereas molecular diagnostics, using blood samples, can be added for cats showing mild neurological signs. In the third study, phosphorylated BDV P and previously reported BDV-host protein-protein interactions were detected in cell cultures, as well as in experimentally and naturally infected animals, by the use of an in situ proximity ligation assay. These protein-protein interactions most likely interfere with signaling pathways of the host, enabling BDV to establish a persistent infection. The type II interferon (IFN-!) is an important key factor of the antiviral host immune response, involved in non-cytolytic clearance of BDV. In the final study, IFN-! mRNA expression was studied in feline BD. A high expression was seen in these cats, as compared to non-infected controls. This expression was higher in cats showing mild neurological signs, and in these cats also moderate-severe pathological lesions were found. These data point to more direct effects of BDV in disease development than has previously been considered. In conclusion, this thesis provides an overview of the current knowledge of BDV, and contributes novel data on virus-host interactions and virus detection.