Evidence map›Paper›PMID 38169842›Full record

ArticleCell genomics2023

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

Erica Normandin, Sergio Triana, Siddharth S Raju, Tammy C T Lan, Kim Lagerborg, Melissa Rudy, Gordon C Adams, Katherine C DeRuff, James Logue, David Liu and 22 more

Open access · goldAbstract read
In one paragraph

Article in Cell genomics, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
0.8field-weighted citation impact, top 28% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed, 4 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
  4. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

32 authors at 7 institutions in 2 countries.

Erica NormandinBroad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA.
Sergio TrianaBroad Institute of Harvard and MIT, Cambridge, MA 02142, 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. Electronic address: strianas@broadinstitute.org.
Siddharth S RajuBroad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA.
Tammy C T LanBroad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Department of Molecular and Cellular Biology, Harvard University, Boston, MA, USA.
Kim LagerborgBroad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Harvard Program in Biological and Biomedical Sciences, Harvard Medical School, Boston, MA, USA.
Melissa RudyBroad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
Gordon C AdamsBroad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Division of Infectious Diseases, Massachusetts General Hospital, Boston, MA 02114, USA.
Katherine C DeRuffBroad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
James LogueIntegrated Research Facility, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD 21702, USA.
David LiuIntegrated Research Facility, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD 21702, USA.
Daniel StrebingerBroad Institute of Harvard and MIT, Cambridge, MA 02142, 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.
Arya RaoColumbia University, New York, NY, USA; Harvard/MIT MD-PhD Program, Harvard Medical School, Boston, MA 02115, USA.
Katelyn S MesserBroad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
Molly SacksBroad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
Ricky D AdamsIntegrated Research Facility, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD 21702, USA.
Krisztina JanoskoIntegrated Research Facility, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD 21702, USA.
Dylan KotliarBroad 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.
Rickey ShahBroad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
Ian CrozierClinical Monitoring Research Program Directorate, Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA.
John L RinnDepartment of Biochemistry, University of Colorado Boulder, Boulder, CO 80303, USA.
Marta MeléLife Sciences Department, Barcelona Supercomputing Center, 08034 Barcelona, Catalonia, Spain.
Anna N HonkoIntegrated Research Facility, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD 21702, USA; National Emerging Infectious Diseases Laboratories, Boston University, Boston, MA 02118, USA.
Feng ZhangBroad Institute of Harvard and MIT, Cambridge, MA 02142, 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.
Mehrtash BabadiBroad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
Jeremy LubanBroad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Ragon Institute of MGH, Harvard, and MIT, Cambridge, MA 02139, USA; Program in Molecular Medicine, University of Massachusetts Chan Medical School, Worcester, MA 01655, USA.
Richard S BennettIntegrated Research Facility, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD 21702, USA.
Alex K ShalekBroad Institute of Harvard and MIT, Cambridge, MA 02142, 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.
Nikolaos BarkasBroad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
Aaron E LinBroad Institute of Harvard and MIT, Cambridge, MA 02142, 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.
Lisa E HensleyIntegrated Research Facility, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD 21702, USA. Electronic address: lisa.hensley@usda.gov.
Pardis C SabetiBroad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815-6789, 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. Electronic address: pardis@broadinstitute.org.
Katherine J SiddleBroad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Department of Molecular Microbiology and Immunology, Brown University, Providence, RI 02912, USA. Electronic address: katherine_siddle@brown.edu.
Broad Institute · USNational Institutes of Health · USBarcelona Supercomputing Center · ESBoston University · USFrederick National Laboratory for Cancer Research · USHarvard University · USUniversity of Colorado Boulder · US

Funding

WORK ORDER 126643 B539 EXPAND IC SUITE75N91019D00024 · NIAID · LEIDOS BIOMEDICAL RESEARCH, INC. · PI BRISCOE, LYNN · 2019 to 2025
$3932.6M
Viral Genomics: evolution, spread, and host interactionsU19AI110818 · NIAID · BROAD INSTITUTE, INC. · PI EARL, ASHLEE MIRIAM · 2014 to 2024
$66.5M
Medical Scientist Training ProgramT32GM007753 · NIGMS · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI WALENSKY, LOREN DAVID · 1985 to 2021
$50.0M
Medical Scientist Training ProgramT32GM144273 · NIGMS · HARVARD MEDICAL SCHOOL · PI David Shumway Jones, Jacqueline A. Lees · 2022 to 2026
$14.7M
Insight into the Ebola virus glycoprotein fusion mechanism gleaned from the 2013-2016 epidemic GP-A82V variantR01AI148784 · NIAID · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI LUBAN, JEREMY · 2020 to 2024
$4.1M
An integrated multiplexed genomic assay for low input clinical samples1U24AI118672 · NIAID · BROAD INSTITUTE, INC. · PI SHALEK, ALEX K · 2015 to 2019
$2.0M
NCI NIH HHS 75N91019D00024NCI NIH HHS HHSN261201500003CNCI NIH HHS HHSN261201500003INIAID NIH HHS HHSN272200700016INIAID NIH HHS HHSN272201800013CNIAID NIH HHS R01 AI148784NIAID NIH HHS U19 AI110818NIAID NIH HHS U24 AI118672NIGMS NIH HHS T32 GM007753NIGMS NIH HHS T32 GM144273
6 · The paper itself

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.

Indexed as

EbolavirusHemorrhagic Fever, EbolaHemorrhagic Fevers, ViralAnimalsMacaca mulattadeconvolutionEbola virusEbola virus diseasehemorrhagic fevershost-virus interactionsminigenomenon-human primatestranscriptomicsviral variants

Identifiers

PMID38169842
PMCPMC10759212
OpenAlexW4388871065

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.