# Mapping Bornavirus encephalitis—A comparative study of viral spread and immune response in human and animal dead-end hosts

## TL;DR

This study compares how Borna disease virus 1 causes brain inflammation in humans and animals, revealing species-specific patterns of viral spread and immune response.

## Contribution

The first comprehensive cross-species analysis of BoDV-1-induced neuropathology in human and animal hosts.

## Key findings

- Humans showed highly variable immune responses, while animals exhibited more species-specific patterns of viral spread.
- Across all species, higher viral protein levels were associated with lower immune cell infiltration.
- Species-specific brain regions were consistently affected, such as the hippocampus in horses and frontal cortex in sheep.

## Abstract

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.

Borna disease virus 1 (BoDV-1) is a fatal virus that causes severe brain inflammation in both humans and animals. While the disease has been known in horses and sheep for centuries, it was only recently identified as a cause of deadly encephalitis in humans. In this study, we systematically compared BoDV-1 infections in humans, horses, sheep, and alpacas by analyzing autopsy/necropsy brain tissue. We found distinct patterns of viral spread and immune responses across species. Humans showed highly variable immune responses, while animals exhibited more species-specific patterns. Interestingly, across all species, higher viral protein values were associated with lower immune cell infiltration, suggesting that the immune response may help control viral spread. Our findings provide new insights into how BoDV-1 affects different hosts and may help to improve future diagnostic and treatment strategies. Understanding these species-specific differences could also shed light on how the virus enters and spreads in the brain.