The SUMOylation pathway suppresses arbovirus replication in Aedes aegypti cells

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)

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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 Mertens, Professor Peter and McFarlane, Mr Steven and Boutell, Dr Chris and Stokes, Samuel and Pondeville, Dr Emilie
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 > Institute of Infection Immunity and Inflammation
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

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
171868The basis of agonist and antagonist function at Free Fatty Acid receptor 2Graeme MilliganBiotechnology and Biological Sciences Research Council (BBSRC)BB/J013854/1MCSB - Molecular Pharmacology
656551Arbovirus interactions with arthropod hostsAlain KohlMedical Research Council (MRC)MC_UU_12014/8MVLS III - CENTRE FOR VIRUS RESEARCH
656521The role of ubiquitin and ubiquitin-like proteins during viral infectionChris BoutellMedical Research Council (MRC)MC_UU_12014/5MVLS III - CENTRE FOR VIRUS RESEARCH