Royle, J. , Ramírez-Santana, C., Akpunarlieva, S., Donald, C. L. , Gestuveo, R. J., Anaya, J.-M., Merits, A., Burchmore, R. , Kohl, A. and Varjak, M. (2020) Glucose-regulated protein 78 interacts with Zika virus envelope protein and contributes to a productive infection. Viruses, 12(5), 524. (doi: 10.3390/v12050524)
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209877.pdf - Published Version Available under License Creative Commons Attribution. 2MB |
Publisher's URL: https://www.mdpi.com/1999-4915/12/5/524
Abstract
Zika virus (ZIKV; Flaviviridae) is a mosquito-borne flavivirus shown to cause fetal abnormalities collectively known as congenital Zika syndrome and Guillain-Barré syndrome in recent outbreaks. Currently, there is no specific treatment or vaccine available, and more effort is needed to identify cellular factors in the viral life cycle. Here, we investigated interactors of ZIKV envelope (E) protein by combining protein pull-down with mass spectrometry. We found that E interacts with the endoplasmic reticulum (ER) resident chaperone, glucose regulated protein 78 (GRP78). Although other flaviviruses are known to co-opt ER resident proteins, including GRP78, to enhance viral infectivity, the role ER proteins play during the ZIKV life cycle is yet to be elucidated. We showed that GRP78 levels increased during ZIKV infection and localised to sites coincident with ZIKV E staining. Depletion of GRP78 using specific siRNAs significantly reduced reporter-virus luciferase readings, viral protein synthesis, and viral titres. Additionally, GRP78 depletion reduced the ability of ZIKV to disrupt host cell translation and altered the localisation of viral replication factories, though there was no effect on viral RNA synthesis. In summary, we showed GRP78 is a vital host-factor during ZIKV infection, which may be involved in the coordination of viral replication factories.
| Item Type: | Articles |
|---|---|
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Akpunarlieva, Miss Snezhana and Gestuveo, Dr Rommel and Royle, Jamie and Donald, Dr Claire and Burchmore, Dr Richard and Varjak, Dr Margus and Kohl, Professor Alain |
| Creator Roles: | Royle, J.Conceptualization, Validation, Formal analysis, Investigation, Data curation, Writing – original draft, Writing – review and editing, Visualization Akpunarlieva, S.Methodology, Software, Investigation, Resources, Writing – review and editing Donald, C. L.Investigation, Writing – review and editing Gestuveo, R. J.Investigation, Writing – review and editing Burchmore, R.Conceptualization, Methodology, Software, Formal analysis, Resources, Data curation, Writing – review and editing, Supervision, Project administration, Funding acquisition Kohl, A.Conceptualization, Formal analysis, Data curation, Writing – original draft, Writing – review and editing, Supervision, Project administration, Funding acquisition Varjak, M.Conceptualization, Formal analysis, Data curation, Writing – original draft, Writing – review and editing, Supervision, Project administration |
| Authors: | Royle, J., Ramírez-Santana, C., Akpunarlieva, S., Donald, C. L., Gestuveo, R. J., Anaya, J.-M., Merits, A., Burchmore, R., Kohl, A., and Varjak, M. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Infection & Immunity College of Medical Veterinary and Life Sciences > School of Molecular Biosciences College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research |
| Journal Name: | Viruses |
| Publisher: | MDPI |
| ISSN: | 1999-4915 |
| ISSN (Online): | 1999-4915 |
| Published Online: | 09 May 2020 |
| Copyright Holders: | Copyright © 2020 The Authors |
| First Published: | First published in Viruses 12(5): 524 |
| Publisher Policy: | Reproduced under a Creative Commons License |
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