Stokes, S., Almire, F., Tatham, M. H., McFarlane, S., Mertens, P., Pondeville, E. and Boutell, C. (2020) The SUMOylation pathway suppresses arbovirus replication in Aedes aegypti cells. PLoS Pathogens, 16(12), e1009134. (doi: 10.1371/journal.ppat.1009134) (PMID:33351855) (PMCID:PMC7802965)
![[img]](https://eprints.gla.ac.uk/style/images/fileicons/text.png) |
Text
226074.pdf - Published Version Available under License Creative Commons Attribution. 3MB |
Abstract
Mosquitoes are responsible for the transmission of many clinically important arboviruses that cause significant levels of annual mortality and socioeconomic health burden worldwide. Deciphering the mechanisms by which mosquitoes modulate arbovirus infection is crucial to understand how viral-host interactions promote vector transmission and human disease. SUMOylation is a post-translational modification that leads to the covalent attachment of the Small Ubiquitin-like MOdifier (SUMO) protein to host factors, which in turn can modulate their stability, interaction networks, sub-cellular localisation, and biochemical function. While the SUMOylation pathway is known to play a key role in the regulation of host immune defences to virus infection in humans, the importance of this pathway during arbovirus infection in mosquito vectors, such as Aedes aegypti (Ae. aegypti), remains unknown. Here we characterise the sequence, structure, biochemical properties, and tissue-specific expression profiles of component proteins of the Ae. aegypti SUMOylation pathway. We demonstrate significant biochemical differences between Ae. aegypti and Homo sapiens SUMOylation pathways and identify cell-type specific patterns of SUMO expression in Ae. aegypti tissues known to support arbovirus replication. Importantly, depletion of core SUMOylation effector proteins (SUMO, Ubc9 and PIAS) in Ae. aegypti cells led to enhanced levels of arbovirus replication from three different families; Zika (Flaviviridae), Semliki Forest (Togaviridae), and Bunyamwera (Bunyaviridae) viruses. Our findings identify an important role for mosquito SUMOylation in the cellular restriction of arboviruses that may directly influence vector competence and transmission of clinically important arboviruses.
| Item Type: | Articles |
|---|---|
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Almire, Ms Floriane and Boutell, Dr Chris and Stokes, Samuel and Pondeville, Dr Emilie and Mertens, Professor Peter and McFarlane, Mr Steven |
| Creator Roles: | Stokes, S.Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Project administration, Validation, Visualization, Writing – original draft, Writing – review and editing Almire, F.Data curation, Formal analysis, Investigation, Methodology, Validation, Visualization, Writing – review and editing McFarlane, S.Resources, Methodology, Supervision Mertens, P.Conceptualization, Supervision Pondeville, E.Conceptualization, Data curation, Formal analysis, Investigation, Funding acquisition, Methodology, Project administration, Supervision, Validation, Visualization, Writing – original draft, Writing – review and editing Boutell, C.Conceptualization, Funding acquisition, Methodology, Project administration, Supervision, Validation, Writing – original draft, Writing – review and editing |
| Authors: | Stokes, S., Almire, F., Tatham, M. H., McFarlane, S., Mertens, P., Pondeville, E., and Boutell, C. |
| College/School: | 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: | PLoS Pathogens |
| Publisher: | Public Library of Science |
| ISSN: | 1553-7366 |
| ISSN (Online): | 1553-7374 |
| Published Online: | 22 December 2020 |
| Copyright Holders: | Copyright © 2020 Stokes et al. |
| First Published: | First published in PLoS Pathogens 16(12): e1009134 |
| Publisher Policy: | Reproduced under a Creative Commons License |
| Data DOI: | 10.5525/gla.researchdata.1084 |
University Staff: Request a correction | Enlighten Editors: Update this record
Funder and Project Information
Funder and Project Information