Forebrain organoids reveal neuronal capacity to elicit protective antiviral responses.

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Presentation Time: 10:45 AM - 11:00 AM
Abstract ID: 5399 - B

Presenting Author:
Seble G Negatu , Immunology PhD Candidate at Univ. of Pennsylvania Perelman Sch. of Med.

Abstract:

Mosquito-borne arboviruses with potential to cause neurotropic disease are a global health threat. These neurotropic viruses are the most common cause of infectious encephalitis (inflammation of the brain), yet our knowledge of antiviral immune regulation at this site remains limited. Neurons are the highly targeted by these viruses and thus must be important mediators of viral replication and spread. Our studies sought to use La Crosse Virus, an emerging arbovirus, to define intrinsic neuronal orchestration of antiviral responses between infected cells and neighboring uninfected bystanders. We observed widespread infection and viral growth in both murine cortical neurons and cerebral organoids. Transcriptomics approaches revealed infection of cortical neurons induced expression of interferon-stimulated genes (ISGs) in both infected and bystander neurons. In forebrain organoids, we found that uninfected bystander neurons have high ISG expression as compared with neighboring infected neurons. Intriguingly, this bystander activation was capable of restricting viral spread. This finding demonstrates that intraneuronal communication mediates protective antiviral response in the CNS. Future directions aim to define the mediators of communication and the protective antiviral signatures using spatial transcriptomics of infected organoid sections.