Duy Janice, Koehler Jeffrey W, Honko Anna N, Schoepp Randal J, Wauquier Nadia, Gonzalez Jean-Paul, Pitt M Louise, Mucker Eric M, Johnson Joshua C, O'Hearn Aileen, Bangura James, Coomber Moinya, Minogue Timothy D
Diagnostic Systems Division, U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, MD, USA.
Virology Division, U.S. Army Medical Institute of Infectious Diseases, Fort Detrick, Frederick, MD, USA.
Sci Rep. 2016 Apr 21;6:24496. doi: 10.1038/srep24496.
Early detection of Ebola virus (EBOV) infection is essential to halting transmission and adjudicating appropriate treatment. However, current methods rely on viral identification, and this approach can misdiagnose presymptomatic and asymptomatic individuals. In contrast, disease-driven alterations in the host transcriptome can be exploited for pathogen-specific diagnostic biomarkers. Here, we present for the first time EBOV-induced changes in circulating miRNA populations of nonhuman primates (NHPs) and humans. We retrospectively profiled longitudinally-collected plasma samples from rhesus macaques challenged via intramuscular and aerosol routes and found 36 miRNAs differentially present in both groups. Comparison of miRNA abundances to viral loads uncovered 15 highly correlated miRNAs common to EBOV-infected NHPs and humans. As proof of principle, we developed an eight-miRNA classifier that correctly categorized infection status in 64/74 (86%) human and NHP samples. The classifier identified acute infections in 27/29 (93.1%) samples and in 6/12 (50%) presymptomatic NHPs. These findings showed applicability of NHP-derived miRNAs to a human cohort, and with additional research the resulting classifiers could impact the current capability to diagnose presymptomatic and asymptomatic EBOV infections.
早期检测埃博拉病毒(EBOV)感染对于阻止传播和判定适当治疗至关重要。然而,目前的方法依赖于病毒鉴定,而这种方法可能会误诊处于症状前期和无症状的个体。相比之下,宿主转录组中由疾病驱动的变化可被用于寻找病原体特异性诊断生物标志物。在此,我们首次展示了EBOV诱导的非人类灵长类动物(NHPs)和人类循环miRNA群体的变化。我们对通过肌肉注射和气溶胶途径感染的恒河猴纵向采集的血浆样本进行回顾性分析,发现两组中均有36种miRNA存在差异。将miRNA丰度与病毒载量进行比较,发现EBOV感染的NHPs和人类共有15种高度相关的miRNA。作为原理验证,我们开发了一种八miRNA分类器,该分类器在64/74(86%)的人类和NHP样本中正确分类了感染状态。该分类器在27/29(93.1%)的样本以及6/12(50%)的症状前期NHPs中识别出急性感染。这些发现表明源自NHP的miRNA适用于人类队列,经过进一步研究,所得分类器可能会影响当前诊断症状前期和无症状EBOV感染的能力。