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.
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