title: Temporal Characterization of Marburg Virus Angola Infection following Aerosol Challenge in Rhesus Macaques.
abstract: Marburg virus (MARV) infection is a lethal hemorrhagic fever for which no licensed vaccines or therapeutics are available. Development of appropriate medical countermeasures requires a thorough understanding of the interaction between the host and the pathogen and the resulting disease course. In this study, 15 rhesus macaques were sequentially sacrificed following aerosol exposure to the MARV variant Angola, with longitudinal changes in physiology, immunology, and histopathology used to assess disease progression. Immunohistochemical evidence of infection and resulting histopathological changes were identified as early as day 3 postexposure (p.e.). The appearance of fever in infected animals coincided with the detection of serum viremia and plasma viral genomes on day 4 p.e. High (>10(7) PFU/ml) viral loads were detected in all major organs (lung, liver, spleen, kidney, brain, etc.) beginning day 6 p.e. Clinical pathology findings included coagulopathy, leukocytosis, and profound liver destruction as indicated by elevated liver transaminases, azotemia, and hypoalbuminemia. Altered cytokine expression in response to infection included early increases in Th2 cytokines such as interleukin 10 (IL-10) and IL-5 and late-stage increases in Th1 cytokines such as IL-2, IL-15, and granulocyte-macrophage colony-stimulating factor (GM-CSF). This study provides a longitudinal examination of clinical disease of aerosol MARV Angola infection in the rhesus macaque model.
  
  
  OBJECTIVE
  In this study, we carefully analyzed the timeline of Marburg virus infection in nonhuman primates in order to provide a well-characterized model of disease progression following aerosol exposure.
authors.affiliation: United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland, USA.
authors.forename: Kenny L
authors.initials: KL
authors.lastname: Lin
authors.affiliation: United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland, USA.
authors.forename: Nancy A
authors.initials: NA
authors.lastname: Twenhafel
authors.affiliation: Boston University School of Medicine and National Emerging Infectious Diseases Laboratory, Boston, Massachusetts, USA.
authors.forename: John H
authors.initials: JH
authors.lastname: Connor
authors.affiliation: United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland, USA.
authors.forename: Kathleen A
authors.initials: KA
authors.lastname: Cashman
authors.affiliation: United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland, USA.
authors.forename: Joshua D
authors.initials: JD
authors.lastname: Shamblin
authors.affiliation: United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland, USA.
authors.forename: Ginger C
authors.initials: GC
authors.lastname: Donnelly
authors.affiliation: United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland, USA.
authors.forename: Heather L
authors.initials: HL
authors.lastname: Esham
authors.affiliation: United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland, USA.
authors.forename: Carly B
authors.initials: CB
authors.lastname: Wlazlowski
authors.affiliation: United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland, USA Integrated Research Facility, National Institute of Allergy and Infectious Diseases, Fort Detrick, Maryland, USA.
authors.forename: Joshua C
authors.initials: JC
authors.lastname: Johnson
authors.affiliation: United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland, USA Integrated Research Facility, National Institute of Allergy and Infectious Diseases, Fort Detrick, Maryland, USA.
authors.forename: Anna N
authors.initials: AN
authors.lastname: Honko
authors.affiliation: United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland, USA.
authors.forename: Miriam A
authors.initials: MA
authors.lastname: Botto
authors.affiliation: Boston University School of Medicine and National Emerging Infectious Diseases Laboratory, Boston, Massachusetts, USA.
authors.forename: Judy
authors.initials: J
authors.lastname: Yen
authors.affiliation: United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland, USA Integrated Research Facility, National Institute of Allergy and Infectious Diseases, Fort Detrick, Maryland, USA.
authors.forename: Lisa E
authors.initials: LE
authors.lastname: Hensley
authors.affiliation: United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland, USA arthur.j.goff.civ@mail.mil.
authors.forename: Arthur J
authors.initials: AJ
authors.lastname: Goff
mesh_terms: D000336:Aerosols; D000818:Animals; D016207:Cytokines / Q000097:blood*; D018450:Disease Progression; D054884:Host-Pathogen Interactions; D007150:Immunohistochemistry; D008137:Longitudinal Studies; D008253:Macaca mulatta; D008379:Marburg Virus Disease / Q000097:blood / Q000503:physiopathology*; D029024:Marburgvirus / Q000472:pathogenicity*; D013997:Time Factors; D019562:Viral Load
chemical_list: D000336:Aerosols; D016207:Cytokines