Sequence variability in viral genome non-coding regions likely contribute to observed differences in viral replication amongst MARV strains

Alonso, Jesus A.

doi:10.1016/j.virol.2013.02.002

Cited by 10 publications

(7 citation statements)

References 34 publications

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“…Amino acid mutations in L may also affect virus adaptation, but these mutations have only been observed in GPA-MARV/Mus [90]. Interestingly, MARV/Mus has been shown to replicate less efficiently than MARV/Ang, so it is possible that these mutations in GPA-MARV/Mus L may affect the efficiency of replication/transcription [119]. Further work will be required to conclusively determine which mutations contribute to virus virulence and to what extent they do so.…”

Section: Rodent-adapted Filoviruses and Their Mutationsmentioning

confidence: 99%

Rodent-Adapted Filoviruses and the Molecular Basis of Pathogenesis

Banadyga

Dolan

Ebihara

2016

Journal of Molecular Biology

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Ebola, Marburg, and Ravn virus, all filoviruses, are the causative agents of severe hemorrhagic fever. Much of what we understand about the pathogenesis of filovirus disease is derived from work with animal models, including non-human primates (NHPs), which are considered the “gold standard” filovirus model since they faithfully recapitulate the clinical hallmarks of filovirus disease. However, rodent models, including the mouse, guinea pig, and hamster, also exist for Ebola, Marburg, and Ravn viruses, and although they may not reproduce all the clinical signs of filovirus disease, thanks to their relative ease-of-use and low cost they are often the first choice for initial descriptions of virus pathogenesis and evaluation of anti-viral prophylactics and therapeutics. Since filoviruses do not cause significant disease in adult, immunocompetent rodents, these models rely on “rodent-adapted” viruses that have been passaged several times through their host until virulence and lethality are achieved. In the process of adaptation, the viruses acquire numerous nucleotide/amino acid mutations that contribute to virulence in their rodent host. Interestingly, virus protein 24 (VP24) and nucleoprotein (NP) appear to be major virulence factors for ebolaviruses in rodents, whereas VP40 appears to be the major virulence factor for marburgviruses. By characterizing these mutations and understanding the molecular mechanisms that lead to the acquisition of virulence, we can gain better insight into the pathogenic processes that underlie filovirus disease in humans. These processes, and the viral and/or cellular proteins that contribute to them, will make attractive targets for the development of novel therapeutics and countermeasures.

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Section: Rodent-adapted Filoviruses and Their Mutationsmentioning

confidence: 99%

Rodent-Adapted Filoviruses and the Molecular Basis of Pathogenesis

Banadyga

Dolan

Ebihara

2016

Journal of Molecular Biology

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“…Elgon variant (MARV/MtE-Mus) as the commonly referred consensus standard. MARV/MtE-Mus, also commonly referred to as “Marburg Musoke” or “MARV/Mus,” was collected in 1980 from a Kenyan survivor who was a physician [ 12 ]. Dr. Musoke contracted Marburg virus from a fatal case (1 death/2 total cases) [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

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

Blair

Keshtkar-Jahromi

Psoter

et al. 2018

Viruses

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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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“…In the rhesus and cynomolgus macaque models, as in the small-animal models using adapted marburgviruses, MARV Angola showed higher virulence compared with other marburgvirus variants, including MARV Musoke, Ci67, Ozolin, and RAVV 140– 143, 149, 154, 159 . The increased virulence of MARV Angola could be explained, at least partially, by an enhanced replication efficiency of this virus, as shown in cell culture experiments 160 . Conflicting results have been reported for RAVV infections of NHPs.…”

Section: Advances In Animal Modeling Of Marburgvirus Infectionsmentioning

confidence: 86%

Recent advances in marburgvirus research

2019

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Marburgviruses are closely related to ebolaviruses and cause a devastating disease in humans. In 2012, we published a comprehensive review of the first 45 years of research on marburgviruses and the disease they cause, ranging from molecular biology to ecology. Spurred in part by the deadly Ebola virus outbreak in West Africa in 2013–2016, research on all filoviruses has intensified. Not meant as an introduction to marburgviruses, this article instead provides a synopsis of recent progress in marburgvirus research with a particular focus on molecular biology, advances in animal modeling, and the use of Egyptian fruit bats in infection experiments.

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Sequence variability in viral genome non-coding regions likely contribute to observed differences in viral replication amongst MARV strains

Cited by 10 publications

References 34 publications

Rodent-Adapted Filoviruses and the Molecular Basis of Pathogenesis

Rodent-Adapted Filoviruses and the Molecular Basis of Pathogenesis

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

Recent advances in marburgvirus research

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