"Dissecting the mechanisms of EV-D68 neuronal pathogenesis"

Christine Vazquez, Sarah E. Hopkins and Kellie A. Jurado

Acute flaccid myelitis (AFM) is a polio-like disease that can affect children who were previously healthy. Although the etiological agent of AFM remains elusive, enterovirus-D68 (EV-D68) has emerged as a likely culprit for AFM. EV-D68 is transmitted through respiratory droplets, yet in some children, can traverse from the lungs to the central nervous system to cause neurological disease, suggesting that EV-D68 may modulate host immune responses for neuronal pathogenesis. Data examining the genomes of several circulating EV-D68 strains over the last ten years in Philadelphia have revealed a polymorphism in the viral 3C protein between the non-neuroinvasive Fermon strain (C92) compared to neuroinvasive EV-D68 strains (Y92). To determine whether this residue impacts immune responses, I examined promoter luciferase signaling and found that a tyrosine at that position can still limit IFN-beta signaling but is instead unable to block IFN-lambda signaling. Further, in neuron-like cells, a neuroinvasive EV-D68 strain is unable to limit IFN-lambda induction compared to the Fermon strain. Taken together, these data suggest that in the context of an EV-D68 strain that is capable of causing neuronal disease, EV-D68 may exploit IFN-lambda signaling for pathogenesis.