The eukaryotic translation elongation factor 1A regulation of actin stress fibers is important for infectious RSV production

Snape, Natale, Li, Dongshe, Wei, Ting, Jin, Hongping, Lor, Mary, Rawle, Daniel J., Spann, Kirsten M., and Harrich, David (2018) The eukaryotic translation elongation factor 1A regulation of actin stress fibers is important for infectious RSV production. Virology Journal, 15. 182.

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Abstract

Cellular protein eukaryotic translation elongation factor 1A (eEF1A) is an actin binding protein that plays a role in the formation of filamentous actin (F-actin) bundles. F-Actin regulates multiple stages of respiratory syncytial virus (RSV) replication including assembly and budding. Our previous study demonstrated that eEF1A knock-down significantly reduced RSV replication. Here we investigated if the eEF1A function in actin bundle formation was important for RSV replication and release. To investigate this, eEF1A function was impaired in HEp-2 cells by either knock-down of eEF1A with siRNA, or treatment with an eEF1A inhibitor, didemnin B (Did B). Cell staining and confocal microscopy analysis showed that both eEF1A knock-down and treatment with Did B resulted in disruption of cellular stress fiber formation and elevated accumulation of F-actin near the plasma membrane. When treated cells were then infected with RSV, there was also reduced formation of virus-induced cellular filopodia. Did B treatment, similarly to eEF1A knock-down, reduced the release of infectious RSV, but unlike eEF1A knock-down, did not significantly affect RSV genome replication. The lower infectious virus production in Did B treated cells also reduced RSV-induced cell death. In conclusion, the cellular factor eEF1A plays an important role in the regulation of F-actin stress fiber formation required for RSV assembly and release.

Item ID: 74891
Item Type: Article (Research - C1)
ISSN: 1743-422X
Keywords: Didemnin B, Eukaryotic translation elongation factor 1A, Respiratory syncytial virus, Stress fibers, Virus replication
Copyright Information: © The Author(s). Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
Funders: National Health and Medical Research Council (NHMRC)
Projects and Grants: NHMRC project grant 1065121
Date Deposited: 12 Jul 2022 02:11
FoR Codes: 32 BIOMEDICAL AND CLINICAL SCIENCES > 3204 Immunology > 320404 Cellular immunology @ 20%
31 BIOLOGICAL SCIENCES > 3101 Biochemistry and cell biology > 310105 Cellular interactions (incl. adhesion, matrix, cell wall) @ 30%
31 BIOLOGICAL SCIENCES > 3107 Microbiology > 310706 Virology @ 50%
SEO Codes: 20 HEALTH > 2001 Clinical health > 200104 Prevention of human diseases and conditions @ 100%
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