The Aedes aegypti Domino orthologue p400 regulates antiviral exogenous small interfering RNA pathway activity and ago-2 expression

McFarlane, M. et al. (2020) The Aedes aegypti Domino orthologue p400 regulates antiviral exogenous small interfering RNA pathway activity and ago-2 expression. mSphere, 5(2), e00081-20. (doi: 10.1128/mSphere.00081-20) (PMID:32269152) (PMCID:PMC7142294)

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Abstract

Arboviruses are pathogens of humans and animals. A better understanding of the interactions between these pathogens and the arthropod vectors, such as mosquitoes, that transmit them is necessary to develop novel control measures. A major antiviral pathway in the mosquito vector is the exogenous small interfering RNA (exo-siRNA) pathway, which is induced by arbovirus-derived double-stranded RNA in infected cells. Although recent work has shown the key role played by Argonaute-2 (Ago-2) and Dicer-2 (Dcr-2) in this pathway, the regulatory mechanisms that govern these pathways have not been studied in mosquitoes. Here, we show that the Domino ortholog p400 has antiviral activity against the alphavirus Semliki Forest virus (Togaviridae) both in Aedes aegypti-derived cells and in vivo. Antiviral activity of p400 was also demonstrated against chikungunya virus (Togaviridae) and Bunyamwera virus (Peribunyaviridae) but not Zika virus (Flaviviridae). p400 was found to be expressed across mosquito tissues and regulated ago-2 but not dcr-2 transcript levels in A. aegypti mosquitoes. These findings provide novel insights into the regulation of an important aedine exo-siRNA pathway effector protein, Ago-2, by the Domino ortholog p400. They add functional insights to previous observations of this protein’s antiviral and RNA interference regulatory activities in Drosophila melanogaster.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Kean, Dr Joy and Gestuveo, Mr Rommel and Loney, Mr Colin and Dietrich, Dr Isabelle and Almire, Ms Floriane and Mcdonald, Dr Melanie and Terry, Mrs Sandra and Schnettler, Dr Esther and Varjak, Dr Margus and Pondeville, Dr Emilie and Mcdonald, Mrs Alma and Donald, Dr Claire and Kohl, Professor Alain
Creator Roles:
McFarlane, M.Conceptualization, Methodology, Formal analysis, Investigation, Validation, Writing – original draft, Writing – review and editing, Visualization, Data curation
Almire, F.Conceptualization, Methodology, Formal analysis, Investigation, Validation, Writing – original draft, Writing – review and editing, Visualization, Data curation
Schnettler, E.Conceptualization, Methodology, Formal analysis, Funding acquisition, Writing – review and editing, Supervision, Project administration, Funding acquisition
Pondeville, E.Conceptualization, Methodology, Formal analysis, Funding acquisition, Investigation, Validation, Writing – original draft, Writing – review and editing, Visualization, Data curation, Supervision, Project administration, Funding acquisition
Kohl, A.Conceptualization, Methodology, Formal analysis, Funding acquisition, Writing – original draft, Writing – review and editing, Visualization, Data curation, Supervision, Project administration, Funding acquisition
Donald, C.Methodology, Investigation, Validation, Writing – review and editing
Varjak, M.Methodology, Formal analysis, Investigation, Validation, Writing – review and editing
Kean, J.Investigation, Validation, Writing – review and editing
Mcdonald, A.Investigation, Validation, Writing – review and editing
Terry, S.Investigation
Gestuveo, R.Investigation
Loney, C.Investigation
Dietrich, I.Resources
Authors: McFarlane, M., Almire, F., Kean, J., Donald, C. L., McDonald, A., Wee, B., Lauréti, M., Varjak, M., Terry, S., Vazeille, M., Gestuveo, R. J., Dietrich, I., Loney, C., Failloux, A.-B., Schnettler, E., Pondeville, E., and Kohl, A.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
College of Medical Veterinary and Life Sciences > Institute of Molecular Cell and Systems Biology
Journal Name:mSphere
Publisher:American Society for Microbiology
ISSN:2379-5042
ISSN (Online):2379-5042
Copyright Holders:Copyright © 2020 McFarlane et al.
First Published:First published in mSphere 5(2):e00081-20
Publisher Policy:Reproduced under a Creative Commons licence
Data DOI:10.5525/gla.researchdata.705

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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
174030DOST-Newton PhD ScholarshipAlain KohlBritish Council (UK) (BRCOU-UK)279705176III-MRC-GU Centre for Virus Research