Department of Pathobiological Sciences, University of Wisconsin - Madison (UW-Madison), Madison, WI 53706, USA.
Biological Sciences Division, Earth and Biological Sciences Directorate, Pacific Northwest National Laboratory (PNNL), Richland, WA 99352, USA.
Cell Host Microbe. 2017 Dec 13;22(6):817-829.e8. doi: 10.1016/j.chom.2017.10.011. Epub 2017 Nov 16.
The pathogenesis of human Ebola virus disease (EVD) is complex. EVD is characterized by high levels of virus replication and dissemination, dysregulated immune responses, extensive virus- and host-mediated tissue damage, and disordered coagulation. To clarify how host responses contribute to EVD pathophysiology, we performed multi-platform 'omics analysis of peripheral blood mononuclear cells and plasma from EVD patients. Our results indicate that EVD molecular signatures overlap with those of sepsis, imply that pancreatic enzymes contribute to tissue damage in fatal EVD, and suggest that Ebola virus infection may induce aberrant neutrophils whose activity could explain hallmarks of fatal EVD. Moreover, integrated biomarker prediction identified putative biomarkers from different data platforms that differentiated survivors and fatalities early after infection. This work reveals insight into EVD pathogenesis, suggests an effective approach for biomarker identification, and provides an important community resource for further analysis of human EVD severity.
人类埃博拉病毒病（EVD）的发病机制复杂。EVD 的特征是病毒复制和传播水平高、免疫反应失调、广泛的病毒和宿主介导的组织损伤以及凝血功能紊乱。为了阐明宿主反应如何导致 EVD 病理生理学的变化，我们对 EVD 患者的外周血单个核细胞和血浆进行了多平台 'omics 分析。我们的结果表明，EVD 的分子特征与败血症的特征重叠，暗示胰腺酶可能导致致命性 EVD 中的组织损伤，并表明埃博拉病毒感染可能诱导异常的中性粒细胞，其活性可以解释致命性 EVD 的特征。此外，整合生物标志物预测从不同数据平台中识别出了感染后早期区分幸存者和死亡者的潜在生物标志物。这项工作揭示了对 EVD 发病机制的深入了解，提出了一种有效的生物标志物识别方法，并为进一步分析人类 EVD 严重程度提供了重要的社区资源。
