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Cell Host Microbe. 2017 Dec 13;22(6):817-829.e8. doi: 10.1016/j.chom.2017.10.011. Epub 2017 Nov 16.

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

Author information

1
Department of Pathobiological Sciences, University of Wisconsin - Madison (UW-Madison), Madison, WI 53706, USA.
2
Biological Sciences Division, Earth and Biological Sciences Directorate, Pacific Northwest National Laboratory (PNNL), Richland, WA 99352, USA.
3
Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai (ISMMS), New York City, NY 10029, USA.
4
Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science (IMS), University of Tokyo, Tokyo 108-8639, Japan.
5
Computing and Analytics Division, National Security Directorate, PNNL, Richland, WA 99352, USA.
6
Department of Chemical and Biological Engineering, UW-Madison, Madison, WI 53706, USA.
7
Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai (ISMMS), New York City, NY 10029, USA; Icahn Institute for Genomics and Multiscale Biology, ISMMS, New York City, NY 10029, USA. Electronic address: harm.vanbakel@mssm.edu.
8
Biological Sciences Division, Earth and Biological Sciences Directorate, Pacific Northwest National Laboratory (PNNL), Richland, WA 99352, USA. Electronic address: thomas.metz@pnnl.gov.
9
Biological Sciences Division, Earth and Biological Sciences Directorate, Pacific Northwest National Laboratory (PNNL), Richland, WA 99352, USA. Electronic address: dick.smith@pnnl.gov.
10
Biological Sciences Division, Earth and Biological Sciences Directorate, Pacific Northwest National Laboratory (PNNL), Richland, WA 99352, USA. Electronic address: katrina.waters@pnnl.gov.
11
Department of Pathobiological Sciences, University of Wisconsin - Madison (UW-Madison), Madison, WI 53706, USA; Department of Biological Sciences, Fourah Bay College, College of Medicine & Allied Health Sciences, University of Sierra Leone, Freetown, Sierra Leone.
12
34(th) Regimental Military Hospital at Wilberforce, Freetown, Sierra Leone. Electronic address: fsahr65@gmail.com.
13
Department of Pathobiological Sciences, University of Wisconsin - Madison (UW-Madison), Madison, WI 53706, USA; Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science (IMS), University of Tokyo, Tokyo 108-8639, Japan; International Research Center for Infectious Diseases, IMS, University of Tokyo, Tokyo 108-8639, Japan. Electronic address: yoshihiro.kawaoka@wisc.edu.

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.

KEYWORDS:

Ebola virus; biomarker; human; inflammation; neutrophils; omics; pancreatitis; pathogenesis; sepsis; systems biology

PMID:
29154144
PMCID:
PMC5730472
DOI:
10.1016/j.chom.2017.10.011
[Indexed for MEDLINE]
Free PMC Article

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