01851nas a2200265   4500000000100000000000100001008004100002260001100043653001800054653001700072653001600089653003100105653001400136653002000150100002000170700003100190700001700221700002600238245006700264856004400331300000800375490000700383520118100390022001401571       2023                            d  c2023/110aanimal models10abornaviruses10afiloviruses10amicrophysiological systems10aorganoids10aorgans-on-chips1 aLina Widerspick1 aJohanna Friederike Steffen1 aDennis Tappe1 aCésar Muñoz-Fontela00aAnimal Model Alternatives in Filovirus and Bornavirus Research  uhttps://www.mdpi.com/1999-4915/15/1/158  a1580 v153 aThe order Mononegavirales contains a variety of highly pathogenic viruses that may infect humans, including the families Filoviridae, Bornaviridae, Paramyxoviridae, and Rhabodoviridae. Animal models have historically been important to study virus pathogenicity and to develop medical countermeasures. As these have inherent shortcomings, the rise of microphysiological systems and organoids able to recapitulate hallmarks of the diseases caused by these viruses may have enormous potential to add to or partially replace animal modeling in the future. Indeed, microphysiological systems and organoids are already used in the pharmaceutical R&D pipeline because they are prefigured to overcome the translational gap between model systems and clinical studies. Moreover, they may serve to alleviate ethical concerns related to animal research. In this review, we discuss the value of animal model alternatives in human pathogenic filovirus and bornavirus research. The current animal models and their limitations are presented followed by an overview of existing alternatives, such as organoids and microphysiological systems, which might help answering open research questions.  a1999-4915