Neuropathology, pathomechanism, and transmission in zoonotic Borna disease virus 1 infection: a systematic review.

Neuropathology, pathomechanism, and transmission in zoonotic Borna disease virus 1 infection: a systematic review

Overview of the Research

• The study systematically reviews current knowledge on Borna disease virus 1 (BoDV-1), which causes severe encephalitis, primarily in horses, sheep, and humans.
• It focuses on BoDV-1’s transmission, entry portals, excretion routes, lesion patterns, immunological responses, and pathogenetic mechanisms in both reservoir and dead-end hosts.
• The review highlights gaps in understanding, particularly regarding human infections, and outlines directions for future research.

Background and Significance

• Borna disease is a neurological disease known for over 200 years, affecting mainly horses and sheep with severe brain inflammation (encephalitis).
• Borna disease virus 1 (BoDV-1) has recently been identified as a cause of fatal encephalitis in humans, marking it as a zoonotic pathogen (transmitted from animals to humans).
• Understanding transmission routes, how the virus enters and spreads within hosts, and the host immune response is crucial for managing and preventing infections.

Research Methods

• Systematic literature search conducted using databases: PubMed, ScienceDirect, and EBSCO.
• Time frame: January 1, 2000 to April 30, 2024.
• A total of 823 records were initially identified; after screening, 41 studies were selected for detailed analysis.

Key Findings on Transmission and Pathogenesis

• The exact mechanisms of BoDV-1 transmission to humans remain poorly understood.
• Potential entry portals of the virus into the body and central nervous system (CNS) are not clearly identified.
• In animal reservoir hosts (e.g., certain wildlife species), some transmission routes and spread patterns within the CNS are better characterized, but many hypotheses remain unconfirmed.
• Evidence suggests BoDV-1 spreads throughout the CNS, but the pathways and dynamics, especially in humans, require further elucidation.

Neuropathological and Immunological Insights

• Histopathological examinations reveal characteristic brain lesions in infected animals and humans, though human data is sparse.
• Lesion distribution in the CNS correlates with severe neurological symptoms and fatal outcomes in humans and animals.
• The immune response to BoDV-1 involves both cellular and humoral components, but detailed immunopathogenesis is not yet fully defined.

Gaps in Knowledge and Future Directions

• Significant knowledge gaps exist about the initial site of viral entry and the exact route of spread within dead-end hosts, including humans.
• Further investigations are needed to identify viral shedding and excretion routes to assess infectiousness and transmission risk.
• Better understanding of pathogenesis could improve diagnosis, treatment, and preventive measures for BoDV-1 infections.
• Animal studies offer valuable insights, but more translational research is necessary to draw parallels relevant to human disease.
• Future research should prioritize:
  • Identifying entry portals in humans
  • Mapping viral dissemination pathways in the CNS
  • Clarifying lesion patterns and immune response mechanisms
  • Developing diagnostic and therapeutic strategies

Conclusion

• This comprehensive review synthesizes current evidence on the neuropathology and transmission of BoDV-1 across species.
• While animal infections offer some model understanding, human infection mechanisms require more research to reduce fatal outcomes.
• Informing future studies with these insights will enhance public health efforts against this emerging zoonotic encephalitis.