Temporal Characterization of Marburg Virus Angola Infection following Aerosol Challenge in Rhesus Macaques.
Kenny L Lin, Nancy A Twenhafel, John H Connor, Kathleen A Cashman, Joshua D Shamblin, Ginger C Donnelly, Heather L Esham, Carly B Wlazlowski, Joshua C Johnson, Anna N Honko, Miriam A Botto, Judy Yen, Lisa E Hensley, Arthur J Goff
Author Information
Kenny L Lin: United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland, USA.
Nancy A Twenhafel: United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland, USA.
John H Connor: Boston University School of Medicine and National Emerging Infectious Diseases Laboratory, Boston, Massachusetts, USA.
Kathleen A Cashman: United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland, USA.
Joshua D Shamblin: United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland, USA.
Ginger C Donnelly: United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland, USA.
Heather L Esham: United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland, USA.
Carly B Wlazlowski: United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland, USA.
Joshua C Johnson: 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.
Anna N Honko: 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.
Miriam A Botto: United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland, USA.
Judy Yen: Boston University School of Medicine and National Emerging Infectious Diseases Laboratory, Boston, Massachusetts, USA.
Lisa E Hensley: 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.
Arthur J Goff: United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland, USA arthur.j.goff.civ@mail.mil.
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 MARVAngolainfection in the rhesus macaque model. IMPORTANCE: In this study, we carefully analyzed the timeline of Marburg virusinfection in nonhuman primates in order to provide a well-characterized model of disease progression following aerosol exposure.
