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

## TL;DR

This study explores how Oropouche virus infects and replicates in different types of neural cells, shedding light on its potential to cause neurological disease.

## Contribution

The study introduces a new ex vivo rat brain slice model and compares replication kinetics of historic and emerging OROV strains in neural cells.

## Key findings

- OROV replicates in neurons, microglia, and astrocytes with strain-specific kinetics.
- Ex vivo rat brain slice cultures are permissive to OROV infection and produce antiviral cytokines.
- Emerging OROV strains show distinct replication patterns compared to historical strains.

## Abstract

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.

Oropouche fever is a recently re-emerging disease caused by infection with Oropouche virus (OROV). Historically, OROV has been overlooked and underreported, and human disease was thought to be self-limiting. However, 2024 saw an unprecedented increase in cases and spread beyond Brazil, including an increased incidence of neurological disease in confirmed patients. Remarkably, very little is known about permissivity and cellular tropism of OROV for cells in the central nervous system. In this study, we characterize OROV viral replication kinetics in central nervous system cell types, including immortalized, primary, and induced pluripotent stem cell-derived cells. A comparison between a historical OROV strain and emerging isolates provides an initial characterization of neuropathogenesis.