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 > School of Infection & Immunity College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research |
| 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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