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

Paul W. Blair, Maryam Keshtkar-Jahromi, Kevin Psoter, Ronald B. Reisler, Travis K. Warren, Sara C. Johnston, Arthur J. Goff, Lydia G. Downey, Sina Bavari, Anthony P. Cardile

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
JournalViruses
Volume10
Issue number11
DOIs
StatePublished - Nov 21 2018

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Marburgvirus
Angola
Macaca
Survival Analysis
Virulence
Exanthema
Animal Disease Models
Macaca fascicularis
Viremia
Anorexia
Appetite
Primates
Communicable Diseases
Biomedical Research
Consensus
Retrospective Studies
Phenotype
Research

Keywords

  • Angola
  • animal
  • filoviridae
  • hemorrhagic fevers
  • Marburg virus disease
  • marburgvirus
  • models
  • mononegavirales
  • Musoke
  • viral

ASJC Scopus subject areas

  • Infectious Diseases
  • Virology

Cite this

Virulence of Marburg Virus Angola Compared to Mt. Elgon (Musoke) in Macaques : A Pooled Survival Analysis. / Blair, Paul W.; Keshtkar-Jahromi, Maryam; Psoter, Kevin; Reisler, Ronald B.; Warren, Travis K.; Johnston, Sara C.; Goff, Arthur J.; Downey, Lydia G.; Bavari, Sina; Cardile, Anthony P.

In: Viruses, Vol. 10, No. 11, 21.11.2018.

Research output: Contribution to journalArticle

Blair, PW, Keshtkar-Jahromi, M, Psoter, K, Reisler, RB, Warren, TK, Johnston, SC, Goff, AJ, Downey, LG, Bavari, S & Cardile, AP 2018, 'Virulence of Marburg Virus Angola Compared to Mt. Elgon (Musoke) in Macaques: A Pooled Survival Analysis', Viruses, vol. 10, no. 11. https://doi.org/10.3390/v10110658
Blair, Paul W. ; Keshtkar-Jahromi, Maryam ; Psoter, Kevin ; Reisler, Ronald B. ; Warren, Travis K. ; Johnston, Sara C. ; Goff, Arthur J. ; Downey, Lydia G. ; Bavari, Sina ; Cardile, Anthony P. / Virulence of Marburg Virus Angola Compared to Mt. Elgon (Musoke) in Macaques : A Pooled Survival Analysis. In: Viruses. 2018 ; Vol. 10, No. 11.
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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.",
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