EV-D68 strains from the 2014 epidemic have acquired the capacity to infect human neuronal cells

What is it about?

Enterovirus D-68 (EV-D68) has been associated with cases of acute flaccid myelitis (AFM), a polio-like illness that predominantly (>90% cases) affects children producing lower motor neuron pattern of flaccid limb weakness. Selected strains of EV-D68 isolated in 2014 and belonging to clades B1, B2 and D1, can infect , replicate in and cause cytopathic effect (CPE) in human neuronal cells (SH-SY5Y). The capacity of these strains to replicate in SH-SY5Y cells parallels their capacity to cause paralysis in mice after intramuscular injection and to spread to and replicate in the spinal cord. By contrast strains similar to the historic prototypic Fermon strain (VR1197) or belonging to clade A (USAN0051U5/2012) fail to replicate in SH-SY5Y cells and do not spread to the spinal cord or cause paralysis in mice. Similar results were seen in primary human fetal brain-derived neurons. Transfection of full-length genomic RNA of strains not able to naturally infect SH-SY5Y cells allowed for production of infectious virus suggesting that viral entry could be a key step in the differential neurotropism of EV-D68 strains. Although all EV D68 strains bound similarly to HeLa cells at 4 degrees C. the neurotropic strains bound ~ 100-fold better than non-neuotropic strains to SH-SY5Y cells.

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Why is it important?

These studies add to our understanding of the neurotropism of EV-D68 strains and suggest that the ability to infect human neuronal-like cells correlates with the capacity of viruses to produce an AFM-like disease in mice. Differences in neuronotropism of EV-D68 strains are due, at least in part, to differences in their capacity to attach to and enter neuronal cells. Non-neuotropic viruses were able to produce infectious progeny following transfection into SH-SY5Y cells but virions from these strains bound ~100-fold less efficiently to these cells than neurotropic strains.

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