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Title: 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.

Authors:
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Publication Date:
Research Org.:
Pacific Northwest National Laboratory (PNNL), Richland, WA (US), Environmental Molecular Sciences Laboratory (EMSL)
Sponsoring Org.:
USDOE
OSTI Identifier:
1414525
Report Number(s):
PNNL-SA-120881
Journal ID: ISSN 1931-3128; 48199; WN9030198
DOE Contract Number:
AC05-76RL01830
Resource Type:
Journal Article
Resource Relation:
Journal Name: Cell Host & Microbe; Journal Volume: 22; Journal Issue: 6
Country of Publication:
United States
Language:
English
Subject:
Environmental Molecular Sciences Laboratory

Citation Formats

Eisfeld, Amie J., Halfmann, Peter J., Wendler, Jason P., Kyle, Jennifer E., Burnum-Johnson, Kristin E., Peralta, Zuleyma, Maemura, Tadashi, Walters, Kevin B., Watanabe, Tokiko, Fukuyama, Satoshi, Yamashita, Makoto, Jacobs, Jon M., Kim, Young-Mo, Casey, Cameron P., Stratton, Kelly G., Webb-Robertson, Bobbie-Jo M., Gritsenko, Marina A., Monroe, Matthew E., Weitz, Karl K., Shukla, Anil K., Tian, Mingyuan, Neumann, Gabriele, Reed, Jennifer L., van Bakel, Harm, Metz, Thomas O., Smith, Richard D., Waters, Katrina M., N'jai, Alhaji, Sahr, Foday, and Kawaoka, Yoshihiro. Multi-platform ’Omics Analysis of Human Ebola Virus Disease Pathogenesis. United States: N. p., 2017. Web. doi:10.1016/j.chom.2017.10.011.
Eisfeld, Amie J., Halfmann, Peter J., Wendler, Jason P., Kyle, Jennifer E., Burnum-Johnson, Kristin E., Peralta, Zuleyma, Maemura, Tadashi, Walters, Kevin B., Watanabe, Tokiko, Fukuyama, Satoshi, Yamashita, Makoto, Jacobs, Jon M., Kim, Young-Mo, Casey, Cameron P., Stratton, Kelly G., Webb-Robertson, Bobbie-Jo M., Gritsenko, Marina A., Monroe, Matthew E., Weitz, Karl K., Shukla, Anil K., Tian, Mingyuan, Neumann, Gabriele, Reed, Jennifer L., van Bakel, Harm, Metz, Thomas O., Smith, Richard D., Waters, Katrina M., N'jai, Alhaji, Sahr, Foday, & Kawaoka, Yoshihiro. Multi-platform ’Omics Analysis of Human Ebola Virus Disease Pathogenesis. United States. doi:10.1016/j.chom.2017.10.011.
Eisfeld, Amie J., Halfmann, Peter J., Wendler, Jason P., Kyle, Jennifer E., Burnum-Johnson, Kristin E., Peralta, Zuleyma, Maemura, Tadashi, Walters, Kevin B., Watanabe, Tokiko, Fukuyama, Satoshi, Yamashita, Makoto, Jacobs, Jon M., Kim, Young-Mo, Casey, Cameron P., Stratton, Kelly G., Webb-Robertson, Bobbie-Jo M., Gritsenko, Marina A., Monroe, Matthew E., Weitz, Karl K., Shukla, Anil K., Tian, Mingyuan, Neumann, Gabriele, Reed, Jennifer L., van Bakel, Harm, Metz, Thomas O., Smith, Richard D., Waters, Katrina M., N'jai, Alhaji, Sahr, Foday, and Kawaoka, Yoshihiro. Fri . "Multi-platform ’Omics Analysis of Human Ebola Virus Disease Pathogenesis". United States. doi:10.1016/j.chom.2017.10.011.
@article{osti_1414525,
title = {Multi-platform ’Omics Analysis of Human Ebola Virus Disease Pathogenesis},
author = {Eisfeld, Amie J. and Halfmann, Peter J. and Wendler, Jason P. and Kyle, Jennifer E. and Burnum-Johnson, Kristin E. and Peralta, Zuleyma and Maemura, Tadashi and Walters, Kevin B. and Watanabe, Tokiko and Fukuyama, Satoshi and Yamashita, Makoto and Jacobs, Jon M. and Kim, Young-Mo and Casey, Cameron P. and Stratton, Kelly G. and Webb-Robertson, Bobbie-Jo M. and Gritsenko, Marina A. and Monroe, Matthew E. and Weitz, Karl K. and Shukla, Anil K. and Tian, Mingyuan and Neumann, Gabriele and Reed, Jennifer L. and van Bakel, Harm and Metz, Thomas O. and Smith, Richard D. and Waters, Katrina M. and N'jai, Alhaji and Sahr, Foday and Kawaoka, Yoshihiro},
abstractNote = {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.},
doi = {10.1016/j.chom.2017.10.011},
journal = {Cell Host & Microbe},
number = 6,
volume = 22,
place = {United States},
year = {Fri Dec 01 00:00:00 EST 2017},
month = {Fri Dec 01 00:00:00 EST 2017}
}