IMAGINE - Immunology and pathology of human bornavirus encephalitis

• Applicant: Privatdozentin Dr. Friederike Liesche-Starnecker
• Subject Area: Molecular and Cellular Neurology and Neuropathology ; Pathology
• Term: since 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 504757758

In only 30-60% of all cases of encephalitis, a specific etiology can be determined. However, because of its high morbidity and mortality, an early designation of the etiology is essential for successful therapy. This underlines the importance to understand cases of encephalitis along with their triggers and pathogens. Several former unsolved cases of encephalitis were retrospectively elucidated, after it was proven that borna disease virus 1 (BoDV-1) can lead to a fatal human infection. Despite a constantly rising number of detected human bornavirus encephalitis, the common and medical awareness of this disease is still low. But because of the disease’s high lethality, it should be of highest interest to raise the sensibility for BoDV-1 infection. Beyond that, caused by a neurotropic virus, bornavirus encephalitis could serve as pattern disease, that helps to understand viral adaption to a neurogenic environment. Our morphological preliminary studies showed that all examined brains of human bornavirus encephalitis had a uniform histopathological pattern. By a multicenter study of MR imaging, a distinct accentuation of the basal nuclei and the insula in an early state of disease was detected. These results allow the assumption that the route of infection might differ from what is known for animals, where an infection through the olfactory system is assumed. We want to proceed with a detailed characterization of the pathophysiological processes in context of human bornavirus encephalitis with focus on the immunological reaction. In a first step, a quantitative analysis of the involved immune cells in comparison with BoDV-1 infection in animals will be conducted. Moreover, cellular components and surface structures involved in virus distribution and cell invasion shall be identified. In a further work step, a screening for anti-BoDV-1-antibodies in samples of cerebrospinal fluid and serum of patients with neurological symptoms will give valuable information about possible subclinical infections. We offer a comprehensive work plan that concentrates on the morphological and immunological aspects of human bornavirus encephalitis with the aim to understand the pathomechanisms behind this fatal disease.

• DFG Programme: Research Grants