Rxivist combines preprints from bioRxiv with data from Twitter to help you find the papers being discussed in your field. Currently indexing 67,316 bioRxiv papers from 296,340 authors.
Contemporary circulating enterovirus D68 strains show differential viral entry and replication in human neuronal cells
David Michael Brown,
Alison M Hixon,
Lauren M Oldfield,
Suman R Das,
Reed S. Shabman,
Kenneth L Tyler,
Richard H Scheuermann
Posted 25 May 2018
bioRxiv DOI: 10.1101/331116
Posted 25 May 2018
Historically, enterovirus D68 (EV-D68) has primarily been associated with respiratory illnesses. However, in the summers of 2014 and 2016 EV-D68 outbreaks coincided with a spike in polio-like acute flaccid myelitis/paralysis (AFM/AFP) cases. This raised concerns that the EV-D68 virus could be the causative agent of AFM during these recent outbreaks. To assess the neurotropic capacity of EV-D68, we explored the use of the neuroblastoma-derived neuronal cell line, SH-SY5Y, as a tissue culture model to determine if differential infection permissibility is observed for different EV-D68 strains. In contrast to HeLa and A549 cells, which support viral infection of all EV-D68 strains tested, SH-SY5Y cells only supported infection by a subset of contemporary EV-D68 strains, including members from the 2014 outbreak. Viral replication and infectivity in SH-SY5Y was assessed using four different assays - infectious virus production, cytopathic effects, cellular ATP release, and VP1 capsid protein production - with similar results. Similar differential neurotropism was also observed in differentiated SH-SY5Y cells, primary human neuron cultures, and a mouse paralysis model. Using the SH-SY5Y cell culture model, we determined that barriers to viral entry was at least partly responsible for the differential infectivity phenotype, since transfection of genomic RNA into SH-SY5Y generated virions for all EV-D68 isolates, but only a single round of replication was observed from strains which could not directly infect SH-SY5Y. In addition to supporting virus replication and other functional studies, this cell culture model may help confirm epidemiological associations between EV-D68 strains and AFM and allow for the rapid identification of emerging neurotropic strains.
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