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Single-Cell Profiling of Ebola Virus Disease In Vivo Reveals Viral and Host Dynamics.
Kotliar, Dylan; Lin, Aaron E; Logue, James; Hughes, Travis K; Khoury, Nadine M; Raju, Siddharth S; Wadsworth, Marc H; Chen, Han; Kurtz, Jonathan R; Dighero-Kemp, Bonnie; Bjornson, Zach B; Mukherjee, Nilanjan; Sellers, Brian A; Tran, Nancy; Bauer, Matthew R; Adams, Gordon C; Adams, Ricky; Rinn, John L; Melé, Marta; Schaffner, Stephen F; Nolan, Garry P; Barnes, Kayla G; Hensley, Lisa E; McIlwain, David R; Shalek, Alex K; Sabeti, Pardis C; Bennett, Richard S.
Afiliação
  • Kotliar D; Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA; FAS Center for Systems Biology, Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, MA 02138, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Harvard-MIT Division of Health
  • Lin AE; FAS Center for Systems Biology, Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, MA 02138, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Harvard Program in Virology, Harvard Medical School, Boston, MA 02115, USA. Electronic address: alin@broadins
  • Logue J; Integrated Research Facility, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD 21702, USA.
  • Hughes TK; Broad Institute of MIT and Harvard, 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
  • Khoury NM; FAS Center for Systems Biology, Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, MA 02138, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Raju SS; Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA; FAS Center for Systems Biology, Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, MA 02138, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Wadsworth MH; Broad Institute of MIT and Harvard, 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.
  • Chen H; Department of Pathology, Stanford University, Stanford, CA 94305, USA.
  • Kurtz JR; Integrated Research Facility, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD 21702, USA.
  • Dighero-Kemp B; Integrated Research Facility, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD 21702, USA.
  • Bjornson ZB; Department of Pathology, Stanford University, Stanford, CA 94305, USA.
  • Mukherjee N; Department of Pathology, Stanford University, Stanford, CA 94305, USA.
  • Sellers BA; Trans-NIH Center for Human Immunology, Autoimmunity, and Inflammation, National Institutes of Health, Bethesda, MD 20814, USA.
  • Tran N; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Ragon Institute of MGH, Harvard, and MIT, Cambridge, MA 02139, USA.
  • Bauer MR; FAS Center for Systems Biology, Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, MA 02138, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Adams GC; FAS Center for Systems Biology, Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, MA 02138, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Adams R; Integrated Research Facility, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD 21702, USA.
  • Rinn JL; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; BioFrontiers Institute, University of Colorado Boulder, Boulder, CO 80303, USA.
  • Melé M; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Life Sciences Department, Barcelona Supercomputing Center, Barcelona, Catalonia 08034, Spain.
  • Schaffner SF; FAS Center for Systems Biology, Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, MA 02138, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Harvard Universi
  • Nolan GP; Department of Pathology, Stanford University, Stanford, CA 94305, USA.
  • Barnes KG; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Harvard University, Boston, MA 02115, USA; MRC-University of Glasgow Centre for Virus Research, Glasgow G61 1QH, UK.
  • 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@nih.gov.
  • McIlwain DR; Department of Pathology, Stanford University, Stanford, CA 94305, USA. Electronic address: mcilwain@stanford.edu.
  • Shalek AK; Broad Institute of MIT and Harvard, 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
  • Sabeti PC; FAS Center for Systems Biology, Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, MA 02138, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Harvard Universi
  • Bennett RS; Integrated Research Facility, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD 21702, USA.
Cell ; 183(5): 1383-1401.e19, 2020 11 25.
Article em En | MEDLINE | ID: mdl-33159858
Ebola virus (EBOV) causes epidemics with high mortality yet remains understudied due to the challenge of experimentation in high-containment and outbreak settings. Here, we used single-cell transcriptomics and CyTOF-based single-cell protein quantification to characterize peripheral immune cells during EBOV infection in rhesus monkeys. We obtained 100,000 transcriptomes and 15,000,000 protein profiles, finding that immature, proliferative monocyte-lineage cells with reduced antigen-presentation capacity replace conventional monocyte subsets, while lymphocytes upregulate apoptosis genes and decline in abundance. By quantifying intracellular viral RNA, we identify molecular determinants of tropism among circulating immune cells and examine temporal dynamics in viral and host gene expression. Within infected cells, EBOV downregulates STAT1 mRNA and interferon signaling, and it upregulates putative pro-viral genes (e.g., DYNLL1 and HSPA5), nominating pathways the virus manipulates for its replication. This study sheds light on EBOV tropism, replication dynamics, and elicited immune response and provides a framework for characterizing host-virus interactions under maximum containment.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Doença pelo Vírus Ebola / Ebolavirus / Interações Hospedeiro-Patógeno / Análise de Célula Única Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Ano de publicação: 2020 Tipo de documento: Article
Texto completo
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Doença pelo Vírus Ebola / Ebolavirus / Interações Hospedeiro-Patógeno / Análise de Célula Única Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Ano de publicação: 2020 Tipo de documento: Article