Neural cells are susceptible to historic and recently emerged Oropouche virus strains

Oropouche fever is a re-emerging global viral threat caused by infection with Oropouche virus (OROV). While disease is generally self-limiting, historical and recent reports of neurologic involvement highlight the importance of understanding the neuropathogenesis of OROV. In this study, we characterize viral replication kinetics in neurons, microglia, and astrocytes derived from immortalized, primary, and induced pluripotent stem cell-derived cells, which are all permissive to infection with the prototypic OROV BeAn19991. We demonstrate cell-type dependent replication kinetics with both historic and recently emerged viral strains. Further, we show that ex vivo rat brain slice cultures can be infected by all OROV strains and produce antiviral cytokines and chemokines, which introduces an additional model to study OROV kinetics and tropism in the central nervous system. These findings provide insight into OROV neuropathogenesis and an initial assessment of newly emerged strains.