Abstract
Marburg virus (MARV), a close relative of Ebola virus, is the causative agent of a severe human disease known as Marburg hemorrhagic fever (MHF). No licensed vaccine or therapeutic exists to treat MHF, and MARV is therefore classified as a Tier 1 select agent and a category A bioterrorism agent. In order to develop countermeasures against this severe disease, animal models that accurately recapitulate human disease are required. Here we describe the development of a novel, uniformly lethal Syrian golden hamster model of MHF using a hamster-adapted MARV variant Angola. Remarkably, this model displayed almost all of the clinical features of MHF seen in humans and non-human primates, including coagulation abnormalities, hemorrhagic manifestations, petechial rash, and a severely dysregulated immune response. This MHF hamster model represents a powerful tool for further dissecting MARV pathogenesis and accelerating the development of effective medical countermeasures against human MHF.
Highlights
Marburg virus (MARV), a non-segmented, negative sense RNA virus belonging to the family Filoviridae, has been responsible for causing sporadic outbreaks of hemorrhagic fever throughout central Africa since its discovery in 19671
We have described the development and characterization of a novel Syrian golden hamster model of Marburg hemorrhagic fever (MHF)
Our hamster model accurately recapitulated all the critical clinical hallmarks observed in humans and non-human primates (NHPs) infected with MARV6,8,10,22,23,25–30, making it one of the most accurate small animal disease models developed for MHF to date
Summary
Marburg virus (MARV), a non-segmented, negative sense RNA virus belonging to the family Filoviridae, has been responsible for causing sporadic outbreaks of hemorrhagic fever throughout central Africa since its discovery in 19671. The 2013–2016 EBOV epidemic in West Africa highlighted the significant threat that filovirus outbreaks pose to international public health, yet despite the potential for MARV to cause serious outbreaks[1,3,4], there are still no medically licensed vaccines or therapeutics to treat MHF. The development of such countermeasures requires relevant and well-characterized animal models that closely recapitulate the disease observed in humans. This hamster model of MHF represents the closest approximation of human MHF outside of NHPs, and it will be an invaluable tool in the study of MARV pathogenesis and the development of viral countermeasures
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