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Contemporary Circulating Enterovirus D68 Strains Have Acquired the Capacity for Viral Entry and Replication in Human Neuronal Cells

Enterovirus D68 (EV-D68) has historically 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 EV-D68 could be the causative agent of AFM...

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Autores principales: Brown, David M., Hixon, Alison M., Oldfield, Lauren M., Zhang, Yun, Novotny, Mark, Wang, Wei, Das, Suman R., Shabman, Reed S., Tyler, Kenneth L., Scheuermann, Richard H.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Microbiology 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6191546/
https://www.ncbi.nlm.nih.gov/pubmed/30327438
http://dx.doi.org/10.1128/mBio.01954-18
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author Brown, David M.
Hixon, Alison M.
Oldfield, Lauren M.
Zhang, Yun
Novotny, Mark
Wang, Wei
Das, Suman R.
Shabman, Reed S.
Tyler, Kenneth L.
Scheuermann, Richard H.
author_facet Brown, David M.
Hixon, Alison M.
Oldfield, Lauren M.
Zhang, Yun
Novotny, Mark
Wang, Wei
Das, Suman R.
Shabman, Reed S.
Tyler, Kenneth L.
Scheuermann, Richard H.
author_sort Brown, David M.
collection PubMed
description Enterovirus D68 (EV-D68) has historically 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 EV-D68 could be the causative agent of AFM during these recent outbreaks. To assess the potential neurotropism of EV-D68, we utilized the neuroblastoma-derived neuronal cell line SH-SY5Y as a cell culture model to determine if differential infection 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 isolates from the 2014 outbreak. Viral replication and infectivity in SH-SY5Y were assessed using multiple assays: virus production, cytopathic effects, cellular ATP release, and VP1 capsid protein production. 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 binding and entry were at least partly responsible for the differential infectivity phenotype. 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 that could not directly infect SH-SY5Y. In addition to supporting virus replication and other functional studies, this cell culture model may help identify the signatures of virulence to confirm epidemiological associations between EV-D68 strains and AFM and allow for the rapid identification and characterization of emerging neurotropic strains.
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spelling pubmed-61915462018-10-26 Contemporary Circulating Enterovirus D68 Strains Have Acquired the Capacity for Viral Entry and Replication in Human Neuronal Cells Brown, David M. Hixon, Alison M. Oldfield, Lauren M. Zhang, Yun Novotny, Mark Wang, Wei Das, Suman R. Shabman, Reed S. Tyler, Kenneth L. Scheuermann, Richard H. mBio Research Article Enterovirus D68 (EV-D68) has historically 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 EV-D68 could be the causative agent of AFM during these recent outbreaks. To assess the potential neurotropism of EV-D68, we utilized the neuroblastoma-derived neuronal cell line SH-SY5Y as a cell culture model to determine if differential infection 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 isolates from the 2014 outbreak. Viral replication and infectivity in SH-SY5Y were assessed using multiple assays: virus production, cytopathic effects, cellular ATP release, and VP1 capsid protein production. 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 binding and entry were at least partly responsible for the differential infectivity phenotype. 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 that could not directly infect SH-SY5Y. In addition to supporting virus replication and other functional studies, this cell culture model may help identify the signatures of virulence to confirm epidemiological associations between EV-D68 strains and AFM and allow for the rapid identification and characterization of emerging neurotropic strains. American Society for Microbiology 2018-10-16 /pmc/articles/PMC6191546/ /pubmed/30327438 http://dx.doi.org/10.1128/mBio.01954-18 Text en Copyright © 2018 Brown et al. https://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research Article
Brown, David M.
Hixon, Alison M.
Oldfield, Lauren M.
Zhang, Yun
Novotny, Mark
Wang, Wei
Das, Suman R.
Shabman, Reed S.
Tyler, Kenneth L.
Scheuermann, Richard H.
Contemporary Circulating Enterovirus D68 Strains Have Acquired the Capacity for Viral Entry and Replication in Human Neuronal Cells
title Contemporary Circulating Enterovirus D68 Strains Have Acquired the Capacity for Viral Entry and Replication in Human Neuronal Cells
title_full Contemporary Circulating Enterovirus D68 Strains Have Acquired the Capacity for Viral Entry and Replication in Human Neuronal Cells
title_fullStr Contemporary Circulating Enterovirus D68 Strains Have Acquired the Capacity for Viral Entry and Replication in Human Neuronal Cells
title_full_unstemmed Contemporary Circulating Enterovirus D68 Strains Have Acquired the Capacity for Viral Entry and Replication in Human Neuronal Cells
title_short Contemporary Circulating Enterovirus D68 Strains Have Acquired the Capacity for Viral Entry and Replication in Human Neuronal Cells
title_sort contemporary circulating enterovirus d68 strains have acquired the capacity for viral entry and replication in human neuronal cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6191546/
https://www.ncbi.nlm.nih.gov/pubmed/30327438
http://dx.doi.org/10.1128/mBio.01954-18
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