Animal models for filoviruses include mice, guinea pigs, hamsters and non-human primates. Use of mice, guinea pigs and hamsters are limited due to the requirement for virus to be adapted by serial passaging, allowing for infection to result in fatal disease. Due to this requirement these models have only been developed for Zaire ebolavirus and Marburgvirus. Non-human primates can be used for all filovirus species, however the NHP models have particular practical and ethical problems that limit their experimental use and are expensive.
At the Australian Animal Health Laboratory we have extensive experience in using ferrets as a surrogate human challenge model for several highly pathogenic viruses including influenza A virus and the henipaviruses. With these viruses, ferrets develop disease consistent with that observed in humans and consequently have been used extensively for assessment of therapeutics and vaccines and, pathogenesis studies. Using this experience we decided to assess the potential of ferrets to be used as a model for human ebola virus disease. Ferrets were challenged with a range of doses (1-106 TCID50) of the Mayinga strain of Ebola virus. All ferrets developed an acute and rapidly progressing haemorrhagic disease with all animals reaching humane endpoints 4 - 7 days post challenge, which was dose dependant. At euthanasia, external petechial haemorrhage on the skin and extensive internal haemorrhage was observed. Real-time PCR, virus re-isolation and immunohistochemistry demonstrates wide spread viraemia and systemic disease.
Interestingly, when ferrets were challenged with 1000 TCID50 of Reston virus (Philippines swine isolate) ferrets developed also developed disease, however, this was slower to develop and milder to that observed with Ebola virus.