Human Ebola Virus Disease Pathogenesis Revealed by Multi-Platform 'Omics Analysis Amie J. Eisfeld1, Peter J. Halfmann1, Jason P. Wendler2, Jennifer E. Kyle2, Kristin E. Burnum-Johnson2, Zuleyma Peralta3, Tadashi Maemura4, Kevin B. Walters1,†, Tokiko Watanabe4, Satoshi Fukuyama4, Makoto Yamashita4, Jon M. Jacobs2, Young-Mo Kim2, Cameron P. Casey2, Kelly G. Stratton5, Bobbie-Jo Webb-Robertson5, Marina A. Gritsenko2, Matthew E. Monroe2, Karl K. Weitz2, Anil K. Shukla2, Mingyuan Tian6, Gabriele Neumann1, Jennifer L. Reed6, Harm van Bakel3,7, Thomas O. Metz2, Richard D. Smith2, Katrina M. Waters8, Alhaji N'jai1,9, Foday Sahr10, Yoshihiro Kawaoka1,4,11 1Department of Pathobiological Sciences, University of Wisconsin-Madison (UW-Madison), Madison, WI, USA; 2Biological Sciences Division, Earth and Biological Sciences Directorate, Pacific Northwest National Laboratory (PNNL), Richland, WA, USA; 3Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai (ISMMS), New York City, NY, , USA; 4Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science (IMS), University of Tokyo, Tokyo, Japan; 5Applied Statistics & Computational Modeling, PNNL, Richland, WA, USA; 6Department of Chemical and Biological Engineering, UW-Madison, Madison, WI, USA; 7Icahn Institute for Genomics and Multiscale Biology, ISMMS, New York City, NY, USA; 8Biological Sciences Division, PNNL, Richland, WA, 99352, USA; 9Department of Biological Sciences, Fourah Bay College, College of Medicine & Allied Health Sciences, University of Sierra Leone, Freetown, Sierra Leone; 1034th Regimental Military Hospital at Wilberforce, Freetown, Sierra Leone; 11International Research Center for Infectious Diseases, IMS, University of Tokyo, Tokyo, Japan; †Current affiliation: Drug Development Division, Southern Research, Frederick, MD, USA
Human Ebola virus disease (EVD) is complex, comprising 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 signatures overlap with those of sepsis, suggest that pancreatic enzymes contribute to tissue damage in fatal EVD, and show that EBOV infection induces aberrant neutrophils whose activity may 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.
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