Abstract
Ebola and Marburg hemorrhagic fevers (EHF and MHF) are caused by the Filoviridae family, Ebolavirus and Marburgvirus (ebolavirus and marburgvirus), respectively. These severe diseases have high mortality rates in humans. Although EHF and MHF are endemic to sub-Saharan Africa. A novel filovirus, Lloviu virus, which is genetically distinct from ebolavirus and marburgvirus, was recently discovered in Spain where filoviral hemorrhagic fever had never been reported. The virulence of this virus has not been determined. Ebolavirus and marburgvirus are classified as biosafety level-4 (BSL-4) pathogens and Category A agents, for which the US government requires preparedness in case of bioterrorism. Therefore, preventive measures against these viral hemorrhagic fevers should be prepared, not only in disease-endemic regions, but also in disease-free countries. Diagnostics, vaccines, and therapeutics need to be developed, and therefore the establishment of animal models for EHF and MHF is invaluable. Several animal models have been developed for EHF and MHF using non-human primates (NHPs) and rodents, which are crucial to understand pathophysiology and to develop diagnostics, vaccines, and therapeutics. Rhesus and cynomolgus macaques are representative models of filovirus infection as they exhibit remarkably similar symptoms to those observed in humans. However, the NHP models have practical and ethical problems that limit their experimental use. Furthermore, there are no inbred and genetically manipulated strains of NHP. Rodent models such as mouse, guinea pig, and hamster, have also been developed. However, these rodent models require adaptation of the virus to produce lethal disease and do not mirror all symptoms of human filovirus infection. This review article provides an outline of the clinical features of EHF and MHF in animals, including humans, and discusses how the animal models have been developed to study pathophysiology, vaccines, and therapeutics.
Highlights
The Family Filoviridae includes three accepted genera, Ebolavirus, Marburgvirus, and Cuevavirus (Figure 1) (Kuhn et al, 2011, 2013)
Significant progress has been made in developing animal models, including mice, guinea pigs, hamsters and non-human primates (NHPs), for EHF and MHF
The NHPs are the most feasible model, because they are the only animals that are lethally infected with non-adapted virus isolates and the pathophysiology is close to that demonstrated in patients
Summary
The Family Filoviridae includes three accepted genera, Ebolavirus (ebolavirus), Marburgvirus (marburgvirus), and Cuevavirus (Figure 1) (Kuhn et al, 2011, 2013). It has been demonstrated that the mouse-adapted EBOVbased Syrian golden hamster model shows the most similar clinical and pathological features, including coagulation abnormalities, to those observed in humans and NHPs infected with wild-type EBOV.
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