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Publication Date
5-2025
Abstract
Certain respiratory viruses exhibit neurotropism, allowing them to invade the central nervous system and induce neuroinflammation. Neurotropic respiratory viruses can lead to a variety of symptoms including encephalitis, seizures, and acute flaccid paralysis, among others. Recent research also suggests that even in non-severe cases, long-term neurological sequelae can persist. Despite the known association of these neurotropic respiratory viruses with short- and long-term neurological manifestations, there are significant knowledge gaps regarding the basic mechanisms of neuropathogenesis that, if addressed, could provide a foundation for the development of prevention and treatment interventions. The goal of this study was to establish in vitro models of infection of the central nervous system by neurotropic respiratory viruses. We developed methods to culture both human excitatory neurons as well as a more complex brain organoid consisting of neuronal and non-neuronal cell types, including astrocytes and microglia. Our work revealed that human excitatory neurons could be infected by several neurotropic respiratory viruses including respiratory syncytial virus (RSV) and human metapneumovirus (hMPV). Furthermore, neurons exhibited distinct innate immune responses to each of these viruses. In addition, through both confocal microscopy and single-cell RNA sequencing, we showed that RSV could infect both neuronal and non-neuronal cells in brain organoids. Single cell RNA sequencing data also revealed that there was an enrichment towards infecting neuronal cells. Overall, these in vitro platforms can facilitate research into virus-host interactions for known and emerging neurotropic viruses. These findings will enable us to continue exploring mechanisms of viral entry to investigate potential therapeutics.
Document Type
Poster
Recommended Citation
Greening, Gage; McLennan, Rebecca; Geanes, Eric S.; Khanal, Santosh; Moore, David; Mwitani, Heather; Louiselle, Daniel A.; and Bradley, Todd, "Respiratory syncytial virus and metapneumovirus infect human induced excitatory neurons and trigger an innate immune response" (2025). Research at Children's Mercy Month 2025. 10.
https://scholarlyexchange.childrensmercy.org/research_month2025/10
