Glucose-regulated protein 78 interacts with Zika virus envelope protein and contributes to a productive infection

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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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:Burchmore, Dr Richard and Akpunarlieva, Miss Snezhana and Varjak, Dr Margus and Gestuveo, Mr Rommel and Royle, Jamie and Donald, Dr Claire 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 > Institute of Infection Immunity and Inflammation
College of Medical Veterinary and Life Sciences > Institute of Molecular Cell and Systems Biology
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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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
656551Arbovirus interactions with arthropod hostsAlain KohlMedical Research Council (MRC)MC_UU_12014/8MVLS III - CENTRE FOR VIRUS RESEARCH
172580The emergence of Zika virus in Brazil: investigating prevalence and host responses to design preventive strategiesAlain KohlMedical Research Council (MRC)MR/N017552/1III-MRC-GU Centre for Virus Research