Virulence of Marburg Virus Angola Compared to Mt. Elgon (Musoke) in Macaques: A Pooled Survival Analysis

Angola variant (MARV/Ang) has replaced Mt. Elgon variant Musoke isolate (MARV/MtE-Mus) as the consensus standard variant for Marburg virus research and is regarded as causing a more aggressive phenotype of disease in animal models; however, there is a dearth of published evidence supporting the high...

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Bibliographic Details
Published in:Viruses 2018-11, Vol.10 (11), p.658
Main Authors: Blair, Paul W, Keshtkar-Jahromi, Maryam, Psoter, Kevin J, Reisler, Ronald B, Warren, Travis K, Johnston, Sara C, Goff, Arthur J, Downey, Lydia G, Bavari, Sina, Cardile, Anthony P
Format: Article
Language:English
Subjects:
Angola
animal
Animal models
Animals
Anorexia
Appetite loss
Clinical trials
Disease
Disease Models, Animal
Ebola virus
Epidemics
Exanthema
Experiments
Fatalities
FDA approval
Filoviridae
hemorrhagic fevers
Infectious diseases
Injections, Intramuscular
Laboratory animals
Macaca
Marburg disease
Marburg virus disease
Marburg Virus Disease - pathology
Marburgvirus
Marburgvirus - pathogenicity
Medical laboratories
Medical research
mononegavirales
Musoke
Phenotypes
Product development
Retrospective Studies
Survival Analysis
United States
Vaccines
viral
Viremia
Virulence
Viruses
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Summary:Angola variant (MARV/Ang) has replaced Mt. Elgon variant Musoke isolate (MARV/MtE-Mus) as the consensus standard variant for Marburg virus research and is regarded as causing a more aggressive phenotype of disease in animal models; however, there is a dearth of published evidence supporting the higher virulence of MARV/Ang. In this retrospective study, we used data pooled from eight separate studies in nonhuman primates experimentally exposed with either 1000 pfu intramuscular (IM) MARV/Ang or MARV/MtE-Mus between 2012 and 2017 at the United States Army Medical Research Institute of Infectious Diseases (USAMRIID). Multivariable Cox proportional hazards regression was used to evaluate the association of variant type with time to death, the development of anorexia, rash, viremia, and 10 select clinical laboratory values. A total of 47 cynomolgus monkeys were included, of which 18 were exposed to MARV/Ang in three separate studies and 29 to MARV/MtE-Mus in five studies. Following universally fatal Marburg virus exposure, compared to MARV/MtE-Mus, MARV/Ang was associated with an increased risk of death (HR = 22.10; 95% CI: 7.08, 68.93), rash (HR = 5.87; 95% CI: 2.76, 12.51) and loss of appetite (HR = 35.10; 95% CI: 7.60, 162.18). Our data demonstrate an increased virulence of MARV/Ang compared to MARV/MtE-Mus variant in the 1000 pfu IM cynomolgus macaque model.
ISSN:1999-4915
1999-4915
DOI:10.3390/v10110658