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Multi-platform 'Omics Analysis of Human Ebola Virus Disease Pathogenesis.

ABSTRACT: 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.

SUBMITTER: Eisfeld AJ

PROVIDER: S-EPMC5730472 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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Multi-platform 'Omics Analysis of Human Ebola Virus Disease Pathogenesis.

Eisfeld Amie J AJ Halfmann Peter J PJ Wendler Jason P JP Kyle Jennifer E JE Burnum-Johnson Kristin E KE Peralta Zuleyma Z Maemura Tadashi T Walters Kevin B KB Watanabe Tokiko T Fukuyama Satoshi S Yamashita Makoto M Jacobs Jon M JM Kim Young-Mo YM Casey Cameron P CP Stratton Kelly G KG Webb-Robertson Bobbie-Jo M BM Gritsenko Marina A MA Monroe Matthew E ME Weitz Karl K KK Shukla Anil K AK Tian Mingyuan M Neumann Gabriele G Reed Jennifer L JL van Bakel Harm H Metz Thomas O TO Smith Richard D RD Waters Katrina M KM N'jai Alhaji A Sahr Foday F Kawaoka Yoshihiro Y

Cell host & microbe 20171116 6

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 s ...[more]

PMID: 29154144

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Project description:Ebola virus (EBV) disease (EVD) is a highly virulent systemic disease characterized by an aggressive systemic inflammatory response and impaired vascular and coagulation systems, often leading to uncontrolled hemorrhaging and death. In this study, the proteomes of 38 sequential plasma samples from 12 confirmed EVD patients were analyzed. Of these 12 cases, 9 patients received treatment with interferon beta 1a (IFN-β-1a), 8 survived EVD, and 4 died; 2 of these 4 fatalities had received IFN-β-1a. Our analytical strategy combined three platforms targeting different plasma subproteomes: a liquid chromatography-mass spectrometry (LC-MS)-based analysis of the classical plasma proteome, a protocol that combines the depletion of abundant plasma proteins and LC-MS to detect less abundant plasma proteins, and an antibody-based cytokine/chemokine multiplex assay. These complementary platforms provided comprehensive data on 1,000 host and viral proteins. Examination of the early plasma proteomes revealed protein signatures that differentiated between fatalities and survivors. Moreover, IFN-β-1a treatment was associated with a distinct protein signature. Next, we examined those proteins whose abundances reflected viral load measurements and the disease course: resolution or progression. Our data identified a prognostic 4-protein biomarker panel (histone H1-5, moesin, kininogen 1, and ribosomal protein L35 [RPL35]) that predicted EVD outcomes more accurately than the onset viral load. IMPORTANCE As evidenced by the 2013-2016 outbreak in West Africa, Ebola virus (EBV) disease (EVD) poses a major global health threat. In this study, we characterized the plasma proteomes of 12 individuals infected with EBV, using two different LC-MS-based proteomics platforms and an antibody-based multiplexed cytokine/chemokine assay. Clear differences were observed in the host proteome between individuals who survived and those who died, at both early and late stages of the disease. From our analysis, we derived a 4-protein prognostic biomarker panel that may help direct care. Given the ease of implementation, a panel of these 4 proteins or subsets thereof has the potential to be widely applied in an emergency setting in resource-limited regions.

Dataset Information

Multi-platform 'Omics Analysis of Human Ebola Virus Disease Pathogenesis.

Publications

Multi-platform 'Omics Analysis of Human Ebola Virus Disease Pathogenesis.

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