Borna disease virus 1 (BoDV-1) was just recently shown to cause predominantly fatal encephalitis in humans. Despite its rarity, bornavirus encephalitis (BVE) can be considered a model disease for encephalitic infections caused by neurotropic viruses and understanding its pathomechanism is of utmost relevance. Aim of this study was to compare the extent and distribution pattern of cerebral inflammation with the clinical course of disease, and individual therapeutic procedures. For this, autoptic brain material from seven patients with fatal BVE was included in this study. Tissue was stained immunohistochemically for pan-lymphocytic marker CD45, the nucleoprotein of BoDV-1, as well as glial marker GFAP and microglial marker Iba1. Sections were digitalized and counted for CD45-positive and BoDV-1-positive cells. For GFAP and Iba1, a semiquantitative score was determined. Furthermore, detailed information about the individual clinical course and therapy were retrieved and summarized in a standardized way. Analysis of the distribution of lymphocytes shows interindividual patterns. In contrast, when looking at the BoDV-1-positive glial cells and neurons, a massive viral involvement in the brain stem was noticeable. Three of the seven patients received early high-dose steroids, which led to a significantly lower lymphocytic infiltration of the central nervous tissue and a longer survival compared to the patients who were treated with steroids later in the course of disease. This study highlights the potential importance of early high-dose immunosuppressive therapy in BVE. Our findings hint at a promising treatment option which should be corroborated in future observational or prospective therapy studies.
Borna disease, which is a severe encephalitis that primarily affects horses and sheep, has been recognised for over two centuries. Borna disease virus 1 (BoDV-1) has been identified as a cause of a predominantly fatal encephalitis in humans. Little scientific data exist regarding the virus' transmission, entry portal, and excretion routes. Lesional patterns, immunological responses, and pathogenetic mechanisms remain largely unexplored in both reservoir and dead-end hosts. This systematic review compiles current knowledge on these aspects and provides guidance for future research. PubMed, ScienceDirect, and EBSCO were searched for publications from Jan 1, 2000, to April 30, 2024. 823 records were found, of which 41 studies were included. This systematic review discusses BoDV-1 transmission, pathogenesis, histopathological changes, and immunology in both reservoir and dead-end hosts, with special regard for humans. The exact propagation mechanisms, entry portal, and viral spread within the CNS are not entirely clear in humans. Although more data exist in animals, much remains hypothetical. Future research should focus on identifying potential entry sites and viral spread in dead-end hosts, which could help to clarify the pathogenesis and lesion distribution in the CNS, thereby contributing to a better understanding of BoDV-1 infection in humans and parallels with animal infections.
Borna disease virus 1 (BoDV-1) has long been recognized as a cause of fatal encephalitis in animals and was only recently identified as a zoonotic pathogen causing a similar disease in humans. This study provides the first comprehensive comparative analysis of BoDV-1-induced neuropathology in human and animal end hosts, including horses, sheep, and alpacas. Using immunohistochemical analyses, we investigated the topographical distribution of BoDV-1 and inflammatory responses in the central nervous system across 19 cases. Key findings reveal distinct differences and overlaps between humans and animals. While humans exhibited heterogeneous patterns especially of the lymphocyte infiltration, animals displayed more species-specific inflammation and viral spread patterns. In horses, the hippocampus and basal ganglia were consistently affected, whereas sheep showed predominant involvement of the frontal cortex and stria olfactoria. Alpacas demonstrated a less uniform distribution but highlighted the brainstem and basal ganglia as critical sites. Intriguingly, across all species, a negative association was observed between lymphocyte infiltration and the number of BoDV-1-infected cells. These findings enhance our understanding of BoDV-1 pathogenesis and is a first step of cross-species comparison in unraveling disease mechanisms in BoDV-1 infection. Further research is warranted to elucidate the implications of these findings for therapeutic strategies and to explore the entry and dissemination routes of BoDV-1 in different hosts.
