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Viruses 2018, 10(11), 658; https://doi.org/10.3390/v10110658

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

1
Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
2
Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD 21224, USA
3
United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, MD 21702, USA
*
Author to whom correspondence should be addressed.
Received: 15 October 2018 / Revised: 18 November 2018 / Accepted: 19 November 2018 / Published: 21 November 2018
(This article belongs to the Collection Advances in Ebolavirus, Marburgvirus, and Cuevavirus Research)
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Abstract

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. View Full-Text
Keywords: Marburg virus disease; hemorrhagic fevers; viral; models; animal; filoviridae; mononegavirales; marburgvirus; Angola; Musoke Marburg virus disease; hemorrhagic fevers; viral; models; animal; filoviridae; mononegavirales; marburgvirus; Angola; Musoke
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Blair, P.W.; Keshtkar-Jahromi, M.; Psoter, K.J.; Reisler, R.B.; Warren, T.K.; Johnston, S.C.; Goff, A.J.; Downey, L.G.; Bavari, S.; Cardile, A.P. Virulence of Marburg Virus Angola Compared to Mt. Elgon (Musoke) in Macaques: A Pooled Survival Analysis. Viruses 2018, 10, 658.

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