Mapping Bornavirus encephalitis-A comparative study of viral spread and immune response in human and animal dead-end hosts.
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.
Copyright: © 2025 Vollmuth et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Publication Date: 2025-08-04 PubMed ID: 40758738PubMed Central: PMC12338802DOI: 10.1371/journal.ppat.1013400Google Scholar: Lookup The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
- Journal Article
- Comparative Study
Summary
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Overview
- This research article presents a comparative study of the brain infection caused by Bornavirus (BoDV-1) in humans and various animals (horses, sheep, alpacas) who are considered dead-end hosts.
- The study focuses on the patterns of viral spread within the central nervous system and the corresponding immune response in these species, providing new insights into how this virus affects different hosts.
Background and Objective
- Borna disease virus 1 (BoDV-1) is known historically to cause fatal brain inflammation (encephalitis) in animals but was only recently confirmed as a zoonotic virus affecting humans similarly.
- The aim of the study is to perform the first broad comparison of the neuropathology—i.e., the changes in nervous system tissue—caused by BoDV-1 across humans and key animal hosts (horses, sheep, alpacas).
- This comparison seeks to identify commonalities and species-specific differences in how the virus spreads and triggers immune responses.
Methods
- The study analyzed brain tissue samples from 19 cases infected with BoDV-1, including human and animal subjects.
- Immunohistochemical techniques were used to detect the presence and location of the virus and to characterize inflammatory immune cell infiltration, particularly lymphocytes.
- The spatial distribution of BoDV-1 and immune responses were mapped across various brain regions within the central nervous system (CNS).
Key Findings
- Species-Specific Viral Distribution:
- In horses, viral infection consistently affected the hippocampus and basal ganglia regions of the brain.
- Sheep showed predominant BoDV-1 involvement in the frontal cortex and the stria olfactoria, areas associated with higher cognitive functions and olfactory (smell) pathways.
- Alpacas did not show a uniform distribution pattern but most notably had viral presence in the brainstem and basal ganglia.
- Humans displayed more heterogeneous and less predictable viral distribution patterns compared to animals.
- Immune Response Differences:
- Humans exhibited heterogeneous lymphocyte infiltration patterns, suggesting variable immune activation and inflammatory responses.
- Animals showed species-specific inflammation patterns; for example, consistent types of lymphocyte infiltration localized to particular brain regions.
- Inverse Correlation Between Virus and Immune Cells:
- Across all species, there was a notable negative association between the number of infected cells and the degree of lymphocyte infiltration.
- This suggests that regions with a high viral load tend to have fewer lymphocytes, potentially indicating immune evasion or a mechanism where immune presence reduces viral replication.
Implications and Future Directions
- This study advances understanding of BoDV-1 pathogenesis by revealing both shared and unique aspects of brain infection and immune response across different dead-end hosts.
- By identifying critical brain regions for viral spread and inflammation, the research aids in pinpointing targets for potential therapeutic intervention.
- The inverse relationship between viral load and lymphocyte count reveals complex host-virus interactions that deserve further exploration to clarify mechanisms of immune control or viral persistence.
- Future research is recommended to:
- Investigate the routes of viral entry and dissemination within the CNS for different species.
- Explore how these neuropathological findings translate into clinical presentations and outcomes.
- Develop and test antiviral or immunomodulatory therapies informed by the cross-species comparison of BoDV-1 infection.
Cite This Article
APA
Vollmuth Y, Jungbäck N, Grochowski P, Mögele T, Stark L, Zarrabi NS, Schlegel J, Schaller T, Märkl B, Matiasek K, Liesche-Starnecker F.
(2025).
Mapping Bornavirus encephalitis-A comparative study of viral spread and immune response in human and animal dead-end hosts.
PLoS Pathog, 21(8), e1013400.
https://doi.org/10.1371/journal.ppat.1013400 Publication
Researcher Affiliations
- Department of Neuropathology, Pathology, Medical Faculty, University of Augsburg, Augsburg, Germany.
- Institute of Pathology, School of Medicine and Health, Technical University of Munich, Munich, Germany.
- Department of Pediatrics, Dr. von Hauner Children's Hospital, Ludwig-Maximilians- Universitaet Muenchen, Munich, Germany.
- Department of Neuropathology, Pathology, Medical Faculty, University of Augsburg, Augsburg, Germany.
- Pathology, Medical Faculty, University of Augsburg, Augsburg, Germany.
- Department of Neuropathology, Pathology, Medical Faculty, University of Augsburg, Augsburg, Germany.
- Pathology, Medical Faculty, University of Augsburg, Augsburg, Germany.
- Pathology, Medical Faculty, University of Augsburg, Augsburg, Germany.
- Institute of Pathology, School of Medicine and Health, Technical University of Munich, Munich, Germany.
- Pathology, Medical Faculty, University of Augsburg, Augsburg, Germany.
- Department of Neuropathology, Pathology, Medical Faculty, University of Augsburg, Augsburg, Germany.
- Pathology, Medical Faculty, University of Augsburg, Augsburg, Germany.
- Department of Exercise Physiology, School of Medicine and Health, Technical University of Munich, Munich, Germany.
- Pathology, Medical Faculty, University of Augsburg, Augsburg, Germany.
- Pathology, Medical Faculty, University of Augsburg, Augsburg, Germany.
- Section of Clinical and Comparative Neuropathology, Centre for Clinical Veterinary Medicine, Ludwig-Maximilians-Universitaet Muenchen, Munich, Germany.
- Department of Neuropathology, Pathology, Medical Faculty, University of Augsburg, Augsburg, Germany.
- Pathology, Medical Faculty, University of Augsburg, Augsburg, Germany.
MeSH Terms
- Animals
- Humans
- Sheep
- Borna disease virus / immunology
- Borna disease virus / pathogenicity
- Horses
- Borna Disease / immunology
- Borna Disease / virology
- Borna Disease / pathology
- Male
- Female
- Encephalitis, Viral / immunology
- Encephalitis, Viral / virology
- Encephalitis, Viral / pathology
- Brain / virology
- Brain / immunology
- Brain / pathology
Conflict of Interest Statement
The authors have declared that no competing interests exist.
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