Elucidation of the molecular mechanisms of influenza-associated encephalopathy due to disorder of ATP generation in mitochondria

包括流感相关性脑病(IAE)在内的重症流感以细胞因子风暴和多器官功能衰竭(MOF)为特征，并伴有严重的水肿。然而，细胞因子风暴、高血管通透性和代谢紊乱等因素之间的关系仍不清楚。我们建立了CPT2变异体的基因靶向小鼠模型，分析了严重流感患者不同器官中的ATP水平，发现病毒感染后明显的ATP耗竭。我们的结论是，不同器官的ATP耗竭导致了突发性脑水肿和多器官功能衰竭，并与流感病毒-细胞因子-蛋白酶循环有关。为了解决这个问题，我们建立了一套临床适用的药物和诊断评估策略。

Severe influenza including influenza-associated encephalopathy (IAE) is characterized by cytokine storm and multi-organ failure (MOF) with severe edema. However, the relationship amongst factors, such as cytokine storm, hyper-vascular permeability, and metabolic disorders, remain unclear. We generated gene targeted mouse models of the CPT2 variants, analyzed ATP levels in various organs of severe influenza, and found significant ATP depletion after virus infection. We conclude that ATP depletion in various organs elicited sudden-onset of brain edema and MOF in associated with influenza virus-cytokine-protease cycle. To address this problem, we have established a clinically applicable drugs and diagnostic assessment strategy.