RESUMO
Respiratory syncytial virus (RSV) primarily infects the respiratory epithelium, but growing evidence suggests it may also be responsible for neurological sequelae. In 3D microphysiological peripheral nerve cultures, RSV infected neurons, macrophages, and dendritic cells along two distinct trajectories depending on the initial viral load. Low-level infection was transient, primarily involved macrophages, and induced moderate chemokine release with transient neural hypersensitivity. Infection with higher viral loads was persistent, infected neuronal cells in addition to monocytes, and induced robust chemokine release followed by progressive neurotoxicity. In spinal cord cultures, RSV infected microglia and dendritic cells but not neurons, producing a moderate chemokine expression pattern. The persistence of infection was variable but could be identified in dendritic cells as long as 30 days post-inoculation. This study suggests that RSV can disrupt neuronal function directly through infection of peripheral neurons and indirectly through infection of resident monocytes, and inflammatory chemokines likely mediate both mechanisms.
