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Mammalian orthoreovirus Infection is Enhanced in Cells Pre-Treated with Sodium Arsenite

1
Department of Biological and Environmental Sciences, Le Moyne College, Syracuse, NY 13214 USA
2
J.A. Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA
*
Author to whom correspondence should be addressed.
Viruses 2019, 11(6), 563; https://doi.org/10.3390/v11060563
Received: 21 May 2019 / Revised: 11 June 2019 / Accepted: 13 June 2019 / Published: 18 June 2019
(This article belongs to the Section Animal Viruses)
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Abstract

Following reovirus infection, cells activate stress responses that repress canonical translation as a mechanism to limit progeny virion production. Work by others suggests that these stress responses, which are part of the integrated stress response (ISR), may benefit rather than repress reovirus replication. Here, we report that compared to untreated cells, treating cells with sodium arsenite (SA) to activate the ISR prior to infection enhanced viral protein expression, percent infectivity, and viral titer. SA-mediated enhancement was not strain-specific, but was cell-type specific. While SA pre-treatment of cells offered the greatest enhancement, treatment within the first 4 h of infection increased the percent of cells infected. SA activates the heme-regulated eIF2α (HRI) kinase, which phosphorylates eukaryotic translation initiation factor 2 alpha (eIF2α) to induce stress granule (SG) formation. Heat shock (HS), another activator of HRI, also induced eIF2α phosphorylation and SGs in cells. However, HS had no effect on percent infectivity or viral yield but did enhance viral protein expression. These data suggest that SA pre-treatment perturbs the cell in a way that is beneficial for reovirus and that this enhancement is independent of SG induction. Understanding how to manipulate the cellular stress responses during infection to enhance replication could help to maximize the oncolytic potential of reovirus. View Full-Text
Keywords: reovirus; viral factory; integrated stress response; translation; phosphorylated eIF2α; stress granules; HRI kinase; sodium arsenite; heat shock; salubrinal reovirus; viral factory; integrated stress response; translation; phosphorylated eIF2α; stress granules; HRI kinase; sodium arsenite; heat shock; salubrinal
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Lutz, M.M., IV; Worth, M.P.; Hinchman, M.M.; Parker, J.S.; Ledgerwood, E.D. Mammalian orthoreovirus Infection is Enhanced in Cells Pre-Treated with Sodium Arsenite. Viruses 2019, 11, 563.

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