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Natural history of Ebola virus disease in rhesus monkeys shows viral variant emergence dynamics and tissue-specific host responses

  1. Author:
    Normandin, Erica
    Triana, Sergio
    Raju, Siddharth S
    Lan, Tammy C T
    Lagerborg, Kim
    Rudy, Melissa
    Adams, Gordon C
    DeRuff, Katherine C
    Logue, James
    Liu, David
    Strebinger, Daniel
    Rao, Arya
    Messer, Katelyn S
    Sacks, Molly
    Adams, Ricky D
    Janosko, Krisztina
    Kotliar, Dylan
    Shah, Rickey
    Crozier,Ian
    Rinn, John L
    Melé, Marta
    Honko, Anna N
    Zhang, Feng
    Babadi, Mehrtash
    Luban, Jeremy
    Bennett, Richard S
    Shalek, Alex K
    Barkas, Nikolaos
    Lin, Aaron E
    Hensley, Lisa E
    Sabeti, Pardis C
    Siddle, Katherine J

  2. Author Address

    Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA., Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA., Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA 02142, USA., Department of Chemistry, Institute for Medical Engineering and Sciences (IMES), and Koch Institute for Integrative Cancer Research, MIT, Cambridge, MA 02142, USA., Ragon Institute of MGH, Harvard, and MIT, Cambridge, MA 02139, USA., Department of Molecular and Cellular Biology, Harvard University, Boston, MA, USA., Harvard Program in Biological and Biomedical Sciences, Harvard Medical School, Boston, MA, USA., Division of Infectious Diseases, Massachusetts General Hospital, Boston, MA 02114, USA., Integrated Research Facility, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD 21702, USA., Howard Hughes Medical Institute, Chevy Chase, MD 20815-6789, USA., McGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA., Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA., Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA., Columbia University, New York, NY, USA., Harvard/MIT MD-PhD Program, Harvard Medical School, Boston, MA 02115, USA., Clinical Monitoring Research Program Directorate, Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA., Department of Biochemistry, University of Colorado Boulder, Boulder, CO 80303, USA., Life Sciences Department, Barcelona Supercomputing Center, 08034 Barcelona, Catalonia, Spain., National Emerging Infectious Diseases Laboratories, Boston University, Boston, MA 02118, USA., Program in Molecular Medicine, University of Massachusetts Chan Medical School, Worcester, MA 01655, USA., Harvard Program in Virology, Harvard Medical School, Boston, MA 02115, USA., Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA., Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544, USA., Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, MA 02138, USA., Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA., Department of Molecular Microbiology and Immunology, Brown University, Providence, RI 02912, USA.,
    1. Year: 2023
    2. Date: Dec 13
    3. Epub Date: 2023 11 21
  2. Journal: Cell Genomics
    1. 3
    2. 12
    3. Pages: 100440
  4. Type of Article: Article
  5. Article Number: 100440
  1. Abstract:

    Ebola virus (EBOV) causes Ebola virus disease (EVD), marked by severe hemorrhagic fever; however, the mechanisms underlying the disease remain unclear. To assess the molecular basis of EVD across time, we performed RNA sequencing on 17 tissues from a natural history study of 21 rhesus monkeys, developing new methods to characterize host-pathogen dynamics. We identified alterations in host gene expression with previously unknown tissue-specific changes, including downregulation of genes related to tissue connectivity. EBOV was widely disseminated throughout the body; using a new, broadly applicable deconvolution method, we found that viral load correlated with increased monocyte presence. Patterns of viral variation between tissues differentiated primary infections from compartmentalized infections, and several variants impacted viral fitness in a EBOV/Kikwit minigenome system, suggesting that functionally significant variants can emerge during early infection. This comprehensive portrait of host-pathogen dynamics in EVD illuminates new features of pathogenesis and establishes resources to study other emerging pathogens. © 2023 The Authors.

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  2. DOI: 10.1016/j.xgen.2023.100440
  3. PMID: 38169842
  4. PMCID: PMC10759212
  5. PII : S2666-979X(23)00275-6

Library Notes

  1. Fiscal Year: FY2023-2024
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