Background Borna disease virus 1 (BoDV-1) causes rare but severe zoonotic infections in humans, presenting as severe encephalitis. The case-fatality risk is very high and no effective countermeasures have been established so far. An immunopathology is presumed, while data on immune responses in humans are limited. Evidence of a role of the complement system in various neurological disorders and central nervous viral infections is increasing and specific inhibitors are available as therapeutic options. Methods In this study, we investigated factors of the complement system in the cerebrospinal fluid (CSF) of patients with BoDV-1 infections (n = 17) in comparison to non-inflammatory control CSF samples (n = 11), using a bead-based multiplex assay. In addition, immunohistochemistry was performed using post-mortem brain tissue samples. Results We found an intrathecal elevation of complement factors of all complement pathways and an active cascade during human BoDV-1 infections. The increase of certain complement factors such as C1q was persistent and C3 complement deposits were detected in post-mortem brain sections. Intrathecal complement levels were negatively correlated with survival. Conclusion Further investigations are warranted to clarify, whether targeting the complement cascade by specific inhibitors might be beneficial for patients suffering from severe BoDV-1 encephalitis.

中文翻译：

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博尔纳病病毒1型（BoDV-1）脑炎患者脑脊液中补体因子长期升高

背景博尔纳病病毒 1 (BoDV-1) 会导致人类罕见但严重的人畜共患感染，表现为严重的脑炎。病死风险非常高，目前尚未制定有效的应对措施。推测存在免疫病理学，但人类免疫反应的数据有限。补体系统在各种神经系统疾病和中枢神经病毒感染中发挥作用的证据越来越多，并且可以使用特定的抑制剂作为治疗选择。方法 在这项研究中，我们使用珠子研究了 BoDV-1 感染患者 (n = 17) 的脑脊液 (CSF) 中补体系统的因素，并与非炎症对照 CSF 样本 (n = 11) 进行比较。基于多重测定。此外，还使用死后脑组织样本进行了免疫组织化学分析。结果我们发现在人类 BoDV-1 感染期间，所有补体途径的补体因子鞘内均升高，并且存在活跃的级联反应。某些补体因子（例如 C1q）的增加持续存在，并且在死后脑切片中检测到 C3 补体沉积。鞘内补体水平与生存呈负相关。结论 需要进一步研究来阐明，通过特定抑制剂靶向补体级联是否可能对患有严重 BoDV-1 脑炎的患者有益。