Analysis of Zika virus capsid-Aedes aegypti mosquito interactome reveals pro-viral host factors critical for establishing infection

Gestuveo, R. J., Royle, J., Donald, C. L. , Lamont, D. J., Hutchinson, E. C. , Merits, A., Kohl, A. and Varjak, M. (2021) Analysis of Zika virus capsid-Aedes aegypti mosquito interactome reveals pro-viral host factors critical for establishing infection. Nature Communications, 12, 2766. (doi: 10.1038/s41467-021-22966-8) (PMID:33986255) (PMCID:PMC8119459)

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Abstract

The escalating global prevalence of arboviral diseases emphasizes the need to improve our understanding of their biology. Research in this area has been hindered by the lack of molecular tools for studying virus-mosquito interactions. Here, we develop an Aedes aegypti cell line which stably expresses Zika virus (ZIKV) capsid proteins in order to study virus-vector protein-protein interactions through quantitative label-free proteomics. We identify 157 interactors and show that eight have potentially pro-viral activity during ZIKV infection in mosquito cells. Notably, silencing of transitional endoplasmic reticulum protein TER94 prevents ZIKV capsid degradation and significantly reduces viral replication. Similar results are observed if the TER94 ortholog (VCP) functioning is blocked with inhibitors in human cells. In addition, we show that an E3 ubiquitin-protein ligase, UBR5, mediates the interaction between TER94 and ZIKV capsid. Our study demonstrates a pro-viral function for TER94/VCP during ZIKV infection that is conserved between human and mosquito cells.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Royle, Mr Jamie and Donald, Dr Claire and Gestuveo, Rommel and Varjak, Dr Margus and Hutchinson, Dr Edward and Kohl, Professor Alain
Authors: Gestuveo, R. J., Royle, J., Donald, C. L., Lamont, D. J., Hutchinson, E. C., Merits, A., Kohl, A., and Varjak, M.
College/School:College of Medical Veterinary and Life Sciences
College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Nature Communications
Publisher:Nature Research
ISSN:2041-1723
ISSN (Online):2041-1723
Copyright Holders:Copyright © 2021 The Authors
First Published:First published in Nature Communications 12: 2766
Publisher Policy:Reproduced under a Creative Commons License
Data DOI:10.5525/gla.researchdata.1020

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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
172398Functional investigations of the influenza virus proteomeEdward HutchinsonMedical Research Council (MRC)MR/N008618/1III-MRC-GU Centre for Virus Research
174030DOST-Newton PhD ScholarshipAlain KohlBritish Council (UK) (BRCOU-UK)279705176III-MRC-GU Centre for Virus Research