title: Longitudinal peripheral blood transcriptional analysis of a patient with severe Ebola virus disease.
abstract: The 2013-2015 outbreak of Ebola virus disease in Guinea, Liberia, and Sierra Leone was unprecedented in the number of documented cases, but there have been few published reports on immune responses in clinical cases and their relationships with the course of illness and severity of Ebola virus disease. Symptoms of Ebola virus disease can include severe headache, myalgia, asthenia, fever, fatigue, diarrhea, vomiting, abdominal pain, and hemorrhage. Although experimental treatments are in development, there are no current U.S. Food and Drug Administration-approved vaccines or therapies. We report a detailed study of host gene expression as measured by microarray in daily peripheral blood samples collected from a patient with severe Ebola virus disease. This individual was provided with supportive care without experimental therapies at the National Institutes of Health Clinical Center from before onset of critical illness to recovery. Pearson analysis of daily gene expression signatures revealed marked gene expression changes in peripheral blood leukocytes that correlated with changes in serum and peripheral blood leukocytes, viral load, antibody responses, coagulopathy, multiple organ dysfunction, and then recovery. This study revealed marked shifts in immune and antiviral responses that preceded changes in medical condition, indicating that clearance of replicating Ebola virus from peripheral blood leukocytes is likely important for systemic viral clearance.
authors.affiliation: Viral Pathogenesis and Evolution Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: John C
authors.identifier: 0000-0002-8037-7101
authors.initials: JC
authors.lastname: Kash
authors.affiliation: Institute for Systems Biology, Seattle, WA 98109, USA.
authors.forename: Kathie-Anne
authors.identifier: 0000-0003-1547-6397
authors.initials: KA
authors.lastname: Walters
authors.affiliation: Critical Care Medicine Department, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Jason
authors.identifier: 0000-0002-3305-7084
authors.initials: J
authors.lastname: Kindrachuk
authors.affiliation: Institute for Systems Biology, Seattle, WA 98109, USA.
authors.forename: David
authors.identifier: 0000-0003-4468-2069
authors.initials: D
authors.lastname: Baxter
authors.affiliation: Institute for Systems Biology, Seattle, WA 98109, USA.
authors.forename: Kelsey
authors.identifier: 0000-0001-5955-5391
authors.initials: K
authors.lastname: Scherler
authors.affiliation: Integrated Research Facility, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD 21702, USA.
authors.forename: Krisztina B
authors.identifier: 0000-0002-7624-2167
authors.initials: KB
authors.lastname: Janosko
authors.affiliation: Integrated Research Facility, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD 21702, USA.
authors.forename: Rick D
authors.identifier: 0000-0002-6906-4403
authors.initials: RD
authors.lastname: Adams
authors.affiliation: United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, MD 21702, USA.
authors.forename: Andrew S
authors.identifier: 0000-0003-4697-7928
authors.initials: AS
authors.lastname: Herbert
authors.affiliation: United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, MD 21702, USA.
authors.forename: Rebekah M
authors.identifier: 0000-0001-9370-7555
authors.initials: RM
authors.lastname: James
authors.affiliation: United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, MD 21702, USA.
authors.forename: Spencer W
authors.identifier: 0000-0003-4540-3279
authors.initials: SW
authors.lastname: Stonier
authors.affiliation: Viral Pathogenesis and Evolution Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Memoli
authors.affiliation: United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, MD 21702, USA.
authors.forename: John M
authors.identifier: 0000-0002-0883-5016
authors.initials: JM
authors.lastname: Dye
authors.affiliation: Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Richard T
authors.initials: RT
authors.lastname: Davey
authors.affiliation: Critical Care Medicine Department, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Daniel S
authors.identifier: 0000-0002-1675-1728
authors.initials: DS
authors.lastname: Chertow
authors.affiliation: Viral Pathogenesis and Evolution Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. taubenbergerj@niaid.nih.gov.
authors.forename: Jeffery K
authors.identifier: 0000-0002-9694-7228
authors.initials: JK
authors.lastname: Taubenberger
mesh_terms: D004196:Disease Outbreaks; D029043:Ebolavirus / Q000472:pathogenicity*; D019142:Hemorrhagic Fever, Ebola / Q000097:blood / Q000821:virology*; D006801:Humans; D007962:Leukocytes / Q000378:metabolism*; D008137:Longitudinal Studies; D012367:RNA, Viral / Q000097:blood / Q000235:genetics; D014779:Virus Replication / Q000502:physiology
chemical_list: D012367:RNA, Viral