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

Rommel J. Gestuveo; Jamie Royle; Claire L. Donald; Douglas J. Lamont; Edward C. Hutchinson; Andres Merits; Alain Kohl; Margus Varjak

doi:10.1038/s41467-021-22966-8

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

Rommel J. Gestuveo (Lead / Corresponding author), Jamie Royle, Claire L. Donald, Douglas J. Lamont, Edward C. Hutchinson, Andres Merits, Alain Kohl (Lead / Corresponding author), Margus Varjak (Lead / Corresponding author)

Centre for Advanced Scientific Technologies

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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.

Original language	English
Article number	2766
Number of pages	16
Journal	Nature Communications
Volume	12
DOIs	https://doi.org/10.1038/s41467-021-22966-8
Publication status	Published - 13 May 2021

Keywords

Cell biology
Protein-protein interaction networks
Virus-host interactions

ASJC Scopus subject areas

General Physics and Astronomy
General Chemistry
General Biochemistry,Genetics and Molecular Biology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/s41467-021-22966-8Licence: CC BY

Final Published VersionFinal published version, 5.09 MBLicence: CC BY

Cite this

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

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.",

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author = "Gestuveo, {Rommel J.} and Jamie Royle and Donald, {Claire L.} and Lamont, {Douglas J.} and Hutchinson, {Edward C.} and Andres Merits and Alain Kohl and Margus Varjak",

note = "This work was funded by the UK Medical Research Council (MC_UU_12014/8) for A.K. E.C.H. is funded by an MRC Career Development Award (MR/N008618/1). R.J.G. was supported by a British Council Newton Fund grant, ID 279705176, under the DOST-Newton PhD Scholarship partnership. The grant is funded by the UK Department for Business, Energy and Industrial Strategy, Philippines Department of Science and Technology-Science Education Institute, and the University of the Philippines Visayas and delivered by the British Council.",

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AU - Gestuveo, Rommel J.

AU - Royle, Jamie

AU - Donald, Claire L.

AU - Lamont, Douglas J.

AU - Hutchinson, Edward C.

AU - Merits, Andres

AU - Kohl, Alain

AU - Varjak, Margus

N1 - This work was funded by the UK Medical Research Council (MC_UU_12014/8) for A.K. E.C.H. is funded by an MRC Career Development Award (MR/N008618/1). R.J.G. was supported by a British Council Newton Fund grant, ID 279705176, under the DOST-Newton PhD Scholarship partnership. The grant is funded by the UK Department for Business, Energy and Industrial Strategy, Philippines Department of Science and Technology-Science Education Institute, and the University of the Philippines Visayas and delivered by the British Council.

PY - 2021/5/13

Y1 - 2021/5/13

N2 - 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.

AB - 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.

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

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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