Carl Bannerman

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.

Abstract Neural stem cells have intact innate immune responses that protect them from virus infection and cell death. Yet, viruses can antagonize such responses to establish neuropathogenesis. Using a forebrain organoid model system at two developmental time points, we identified that neural stem cells, in particular radial glia, are basally primed to respond to virus infection by upregulating several antiviral interferon-stimulated genes.

Abstract The capacity of intrinsic neuronal innate immune response to mediate protective antiviral responses remains incomplete. Here, we evaluated the role of intercellular crosstalk in mediating intrinsic neuronal immunity and its contribution to limiting viral infection. We found that in the absence of viral antagonism, neurons transcriptionally induce robust IFN signaling and can effectively signal to neighboring uninfected bystander neurons.