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Natural history of Ebola virus disease in rhesus monkeys shows viral variant emergence dynamics and tissue-specific host responses.
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.
Afiliação
  • Normandin E; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA.
  • Triana S; Broad 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 Ca
  • Raju SS; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA.
  • Lan TCT; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Department of Molecular and Cellular Biology, Harvard University, Boston, MA, USA.
  • Lagerborg K; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Harvard Program in Biological and Biomedical Sciences, Harvard Medical School, Boston, MA, USA.
  • Rudy M; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
  • Adams GC; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Division of Infectious Diseases, Massachusetts General Hospital, Boston, MA 02114, USA.
  • DeRuff KC; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
  • Logue J; Integrated Research Facility, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD 21702, USA.
  • Liu D; Integrated Research Facility, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD 21702, USA.
  • Strebinger D; Broad 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
  • Rao A; Columbia University, New York, NY, USA; Harvard/MIT MD-PhD Program, Harvard Medical School, Boston, MA 02115, USA.
  • Messer KS; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
  • Sacks M; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
  • Adams RD; Integrated Research Facility, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD 21702, USA.
  • Janosko K; Integrated Research Facility, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD 21702, USA.
  • Kotliar D; 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.
  • Shah R; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
  • Crozier I; Clinical Monitoring Research Program Directorate, Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA.
  • Rinn JL; Department of Biochemistry, University of Colorado Boulder, Boulder, CO 80303, USA.
  • Melé M; Life Sciences Department, Barcelona Supercomputing Center, 08034 Barcelona, Catalonia, Spain.
  • Honko AN; Integrated 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.
  • Zhang F; Broad 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
  • Babadi M; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
  • Luban J; Broad 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.
  • Bennett RS; Integrated Research Facility, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD 21702, USA.
  • Shalek AK; Broad 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 Ca
  • Barkas N; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
  • Lin AE; Broad 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,
  • Hensley LE; Integrated 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.
  • Sabeti PC; Broad 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
  • Siddle KJ; Broad 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.
Cell Genom ; 3(12): 100440, 2023 Dec 13.
Article em En | MEDLINE | ID: mdl-38169842
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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Doença pelo Vírus Ebola / Ebolavirus / Febres Hemorrágicas Virais Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: Cell Genom Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Estados Unidos
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Doença pelo Vírus Ebola / Ebolavirus / Febres Hemorrágicas Virais Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: Cell Genom Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Estados Unidos