دورية أكاديمية
A conserved transcriptional response to intranasal Ebola virus exposure in nonhuman primates prior to onset of fever.
| العنوان: | A conserved transcriptional response to intranasal Ebola virus exposure in nonhuman primates prior to onset of fever. |
|---|---|
| المؤلفون: | Speranza E; Department of Microbiology, Bioinformatics Program, National Emerging Infectious Diseases Laboratories, Boston University, Boston, MA 02118, USA., Bixler SL; Molecular and Translational Sciences Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD 21702, USA., Altamura LA; Diagnostic Systems Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD 21702, USA., Arnold CE; Center for Genome Sciences, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD 21702, USA., Pratt WD; Virology Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD 21702, USA., Taylor-Howell C; Diagnostic Systems Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD 21702, USA., Burrows C; Diagnostic Systems Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD 21702, USA., Aguilar W; Diagnostic Systems Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD 21702, USA., Rossi F; Virology Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD 21702, USA., Shamblin JD; Virology Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD 21702, USA., Wollen SE; Virology Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD 21702, USA., Zelko JM; Virology Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD 21702, USA., Minogue T; Diagnostic Systems Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD 21702, USA., Nagle E; Center for Genome Sciences, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD 21702, USA., Palacios G; Center for Genome Sciences, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD 21702, USA. gustavo.f.palacios.ctr@mail.mil arthur.j.goff.civ@mail.mil jhconnor@bu.edu., Goff AJ; Virology Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD 21702, USA. gustavo.f.palacios.ctr@mail.mil arthur.j.goff.civ@mail.mil jhconnor@bu.edu., Connor JH; Department of Microbiology, Bioinformatics Program, National Emerging Infectious Diseases Laboratories, Boston University, Boston, MA 02118, USA. gustavo.f.palacios.ctr@mail.mil arthur.j.goff.civ@mail.mil jhconnor@bu.edu. |
| المصدر: | Science translational medicine [Sci Transl Med] 2018 Mar 28; Vol. 10 (434). |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S. |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Association for the Advancement of Science Country of Publication: United States NLM ID: 101505086 Publication Model: Print Cited Medium: Internet ISSN: 1946-6242 (Electronic) Linking ISSN: 19466234 NLM ISO Abbreviation: Sci Transl Med Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Washington, DC : American Association for the Advancement of Science |
| مواضيع طبية MeSH: | Ebolavirus/*pathogenicity , Hemorrhagic Fever, Ebola/*genetics , Hemorrhagic Fever, Ebola/*virology, Administration, Intranasal ; Animals ; Disease Models, Animal ; Hemorrhagic Fever, Ebola/immunology ; Macaca fascicularis/virology |
| مستخلص: | Ebola virus disease (EVD), caused by Ebola virus (EBOV), is a severe illness characterized by case fatality rates of up to 90%. The sporadic nature of outbreaks in resource-limited areas has hindered the ability to characterize the pathogenesis of EVD at all stages of infection but particularly early host responses. Pathogenesis is often studied in nonhuman primate (NHP) models of disease that replicate major aspects of human EVD. Typically, NHP models use a large infectious dose, are carried out through intramuscular or aerosol exposure, and have a fairly uniform disease course. By contrast, we report our analysis of the host response to EBOV after intranasal exposure. Twelve cynomolgus macaques were infected with 100 plaque-forming units of EBOV/Makona through intranasal exposure and presented with varying times to onset of EVD. We used RNA sequencing and a newly developed NanoString CodeSet to monitor the host response via changes in RNA transcripts over time. When individual animal gene expression data were phased based on the onset of sustained fever, the first clinical sign of severe disease, mathematical models indicated that interferon-stimulated genes appeared as early as 4 days before fever onset. This demonstrates that lethal EVD has a uniform and predictable response to infection regardless of time to onset. Furthermore, expression of a subset of genes could predict disease development before other host-based indications of infection such as fever. (Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.) |
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| معلومات مُعتمدة: | EP-D-15-015 United States EPA EPA; R01 AI096159 United States AI NIAID NIH HHS; R21 AI121933 United States AI NIAID NIH HHS; R21 AI135517 United States AI NIAID NIH HHS |
| تواريخ الأحداث: | Date Created: 20180330 Date Completed: 20190923 Latest Revision: 20230315 |
| رمز التحديث: | 20231215 |
| مُعرف محوري في PubMed: | PMC9986849 |
| DOI: | 10.1126/scitranslmed.aaq1016 |
| PMID: | 29593102 |
| قاعدة البيانات: | MEDLINE |
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