Examined and available brain regions.

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.

博尔纳病病毒1型（Borna disease virus 1, BoDV-1）长期以来被认定为引发动物致死性脑炎的病原体，直至近年才被确认为可导致人类罹患相似疾病的人畜共患病原体。本研究首次针对博尔纳病病毒1型感染人类与多种动物终末宿主（包括马、绵羊与羊驼）后的神经病理变化，开展了全面的比较分析。通过免疫组织化学分析，我们对19例病例的中枢神经系统内博尔纳病病毒1型的拓扑分布与炎症反应进行了系统研究。核心研究结果揭示了人类与动物宿主之间既存在显著差异，也存在一定重叠：人类的淋巴细胞浸润模式呈现明显异质性，而动物则表现出更多物种特异性的炎症与病毒播散模式。具体而言，马的海马体与基底神经节持续受累；绵羊则主要累及额叶皮层与嗅纹；羊驼的病毒分布相对不均一，但脑干与基底神经节为关键受累部位。值得注意的是，在所有受试物种中均观察到淋巴细胞浸润数量与博尔纳病病毒1型感染细胞数呈负相关关系。本研究结果加深了我们对博尔纳病病毒1型致病机制的理解，是通过跨物种比较解析博尔纳病病毒1型感染致病机制的开创性第一步。后续仍需开展进一步研究，以阐明本研究结果对治疗策略的指导意义，并探索博尔纳病病毒1型在不同宿主中的入侵与播散途径。