Oropouche virus disrupts neurodevelopment and exhibits congenital infection potential.
- 1Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
- 2Department of Neuroscience, Mahoney Institute for Neurosciences, Institute for Regenerative Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
- 3Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. [email protected].
Abstract
Oropouche virus (OROV) historically caused a self-limiting disease, yet recent strains have been clinically linked to congenital infection and neurodevelopmental disease. These observations highlight the need to study OROV as a congenital pathogen. Here, using both a historical and currently circulating strain, we show OROV infects neurons across differentiation states in human forebrain organoids. Compared with the neurotropic congenital pathogen Zika virus (ZIKV), OROV exhibits a heightened capacity for neuroinfection and pathology in both forebrain organoids and neonatal mice. The increased permissiveness of OROV is driven, in part, by a broader neuronal tropism and a relative insensitivity to neuronal type I interferon-mediated antiviral responses. Consistent with clinical observations, neonatal neuroinfection results in rapid and severe neuropathology marked by cerebral hemorrhage. Finally, using a transient type I interferon-blockade model, we demonstrate that OROV can productively infect the murine placenta and cause fetal growth restriction. Together, our complementary models support a unified framework in which placental and fetal barriers limit productive fetal brain infection, yet OROV exhibits marked neurotropism and neuropathogenic potential upon gaining access to developing neural tissues. These findings reinforce the need for vigilant monitoring of OROV as an emerging pathogen associated with adverse pregnancy outcomes and congenital disease.
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BibTeX
@article{bannerman2026oropouche,
title = {{Oropouche virus disrupts neurodevelopment and exhibits congenital infection potential.}},
author = {Carl Bannerman and Drake T Philip and Elizabeth A Kennedy and Stephanie Liu and Peter Hewins and Yennifer Barajas and Taylor Miller-Ensminger and Kristen Walsh and Seble G Negatu and Guo-Li Ming and Kellie A Jurado},
journal = {Nature communications},
year = {2026},
month = sep,
doi = {10.1038/s41467-026-77859-5},
url = {https://europepmc.org/article/MED/42907468},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Oropouche virus disrupts neurodevelopment and exhibits congenital infection potential.
AU - Carl Bannerman
AU - Drake T Philip
AU - Elizabeth A Kennedy
AU - Stephanie Liu
AU - Peter Hewins
AU - Yennifer Barajas
AU - Taylor Miller-Ensminger
AU - Kristen Walsh
AU - Seble G Negatu
AU - Guo-Li Ming
AU - Kellie A Jurado
PY - 2026
DA - 2026/09/22
JO - Nature communications
DO - 10.1038/s41467-026-77859-5
UR - https://europepmc.org/article/MED/42907468
AB - Oropouche virus (OROV) historically caused a self-limiting disease, yet recent strains have been clinically linked to congenital infection and neurodevelopmental disease. These observations highlight the need to study OROV as a congenital pathogen. Here, using both a historical and currently circulating strain, we show OROV infects neurons across differentiation states in human forebrain organoids. Compared with the neurotropic congenital pathogen Zika virus (ZIKV), OROV exhibits a heightened capacity for neuroinfection and pathology in both forebrain organoids and neonatal mice. The increased permissiveness of OROV is driven, in part, by a broader neuronal tropism and a relative insensitivity to neuronal type I interferon-mediated antiviral responses. Consistent with clinical observations, neonatal neuroinfection results in rapid and severe neuropathology marked by cerebral hemorrhage. Finally, using a transient type I interferon-blockade model, we demonstrate that OROV can productively infect the murine placenta and cause fetal growth restriction. Together, our complementary models support a unified framework in which placental and fetal barriers limit productive fetal brain infection, yet OROV exhibits marked neurotropism and neuropathogenic potential upon gaining access to developing neural tissues. These findings reinforce the need for vigilant monitoring of OROV as an emerging pathogen associated with adverse pregnancy outcomes and congenital disease.
SN - 2041-1723
ER -