Temporal Characterization of Marburg Virus Angola Infection following Aerosol Challenge in Rhesus Macaques.

Abstract:

UNLABELLED: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. IMPORTANCE: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.

journal_name

J Virol

journal_title

Journal of virology

authors

Lin KL,Twenhafel NA,Connor JH,Cashman KA,Shamblin JD,Donnelly GC,Esham HL,Wlazlowski CB,Johnson JC,Honko AN,Botto MA,Yen J,Hensley LE,Goff AJ

doi

10.1128/JVI.01147-15

subject

Has Abstract

pub_date

2015-10-01 00:00:00

pages

9875-85

issue

19

eissn

0022-538X

issn

1098-5514

pii

JVI.01147-15

journal_volume

89

pub_type

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