Human organoids for Risk Group 4 virus research: a new frontier in investigating Nipah virus infection of the central nervous system.

UNLABELLED: New approach methodologies, such as high-complexity in vitro systems, are increasingly prioritized in biomedical research as potential alternatives to animal experimentation. We show that cerebral organoids derived from human induced pluripotent stem cells can be leveraged to (i) investigate isolate-specific replication dynamics of Nipah virus and (ii) model key histopathological lesions found in the brain tissue of infected human patients. Furthermore, we discuss the importance of organoid models for the study of Risk Group 4 viruses.

IMPORTANCE

Advanced development of medical countermeasures against Risk Group 4 viruses, such as the Nipah virus, historically required testing in mammals under the FDA Animal Rule and translation of data to inform clinical trials in humans. Because the application of human organoids in research on viruses pathogenic for humans is conspecific, it bears the potential to reduce, refine, or replace animal studies where unnecessary. Human cerebral organoids are three-dimensional cell aggregates that resemble the developing human brain functionally and structurally. Brain organoids may be valuable in investigating the replication, neuroinvasion, pathogenesis, virulence, and persistence of neurotropic viruses and provide scientific discernment when developing medical countermeasures destined for the human end-user.