Henipavirus infection causes severe respiratory and neurological disease in humans that can be fatal. To characterize the pathogenic mechanisms of henipavirus infection in vivo, we performed experimental infections in ferrets followed by genome-wide gene expression analysis of lung and brain tissues. The Hendra, Nipah-Bangladesh, and Nipah-Malaysia strains caused severe respiratory and neurological disease with animals succumbing around 7 days post infection. Despite the presence of abundant viral shedding, animal-to-animal transmission did not occur. The host gene expression profiles of the lung tissue showed early activation of interferon responses and subsequent expression of inflammation-related genes that coincided with the clinical deterioration. Additionally, the lung tissue showed unchanged levels of lymphocyte markers and progressive downregulation of cell cycle genes and extracellular matrix components. Infection in the brain resulted in a limited breadth of the host responses, which is in accordance with the immunoprivileged status of this organ. Finally, we propose a model of the pathogenic mechanisms of henipavirus infection that integrates multiple components of the host responses.

肝炎病毒感染会在人类中引起严重的呼吸道和神经系统疾病，可能是致命的。表征体内肝炎病毒感染的致病机制，我们在雪貂中进行了实验性感染，然后对肺和脑组织进行了全基因组基因表达分析。Hendra，Nipah-Bangladesh和Nipah-Malaysia毒株在感染后7天左右死于动物，引起严重的呼吸道和神经系统疾病。尽管存在大量的病毒脱落，但并未发生动物对动物的传播。肺组织的宿主基因表达谱显示干扰素应答的早期激活和炎症相关基因的后续表达，与临床恶化相吻合。另外，肺组织显示出不变的淋巴细胞标志物水平以及细胞周期基因和细胞外基质成分的逐步下调。脑部感染导致宿主反应的范围有限，这符合该器官的免疫特权状态。最后，我们提出了整合了宿主反应的多个组成部分的肝炎病毒感染的致病机制模型。