aBravo is a novel Aedes aegypti antiviral protein that interacts with, but acts independently of, the exogenous siRNA pathway effector Dicer 2

Varjak, M. , Gestuveo, R. J., Burchmore, R. , Schnettler, E. and Kohl, A. (2020) aBravo is a novel Aedes aegypti antiviral protein that interacts with, but acts independently of, the exogenous siRNA pathway effector Dicer 2. Viruses, 12(7), 748. (doi: 10.3390/v12070748)

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Abstract

Mosquitoes, such as Aedes aegypti, can transmit arboviruses to humans. The exogenous short interfering RNA (exo-siRNA) pathway plays a major antiviral role in controlling virus infection in mosquito cells. The Dicer 2 (Dcr2) nuclease is a key effector protein in this pathway, which cleaves viral double-stranded RNA into virus-derived siRNAs that are further loaded onto an effector called Argonaute 2 (Ago2), which as part of the multiprotein RNA-induced silencing complex (RISC) targets and cleaves viral RNA. In order to better understand the effector protein Dcr2, proteomics experiments were conducted to identify interacting cellular partners. We identified several known interacting partners including Ago2, as well as two novel and previously uncharacterized Ae. aegypti proteins. The role of these two proteins was further investigated, and their interactions with Dcr2 verified by co-immunoprecipitation. Interestingly, despite their ability to interact with Ago2 and Piwi4, neither of these proteins was found to affect exo-siRNA silencing in a reporter assay. However, one of these proteins, Q0IFK9, subsequently called aBravo (aedine broadly active antiviral protein), was found to mediate antiviral activity against positive strand RNA arboviruses. Intriguingly the presence of Dcr2 was not necessary for this effect, suggesting that this interacting antiviral effector may act as part of protein complexes with potentially separate antiviral activities.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Schnettler, Dr Esther and Burchmore, Dr Richard and Gestuveo, Mr Rommel and Varjak, Dr Margus and Kohl, Professor Alain
Creator Roles:
Varjak, M.Conceptualization, Methodology, Formal analysis, Investigation, Validation, Resources, Writing – original draft, Writing – review and editing, Visualization, Funding acquisition
Schnettler, E.Conceptualization, Methodology, Resources, Writing – review and editing, Supervision, Project administration, Funding acquisition
Kohl, A.Conceptualization, Methodology, Resources, Writing – original draft, Writing – review and editing, Supervision, Project administration, Funding acquisition
Burchmore, R.Methodology, Resources, Writing – review and editing
Gestuveo, R. J.Investigation, Writing – review and editing, Visualization, Funding acquisition
Authors: Varjak, M., Gestuveo, R. J., Burchmore, R., Schnettler, E., and Kohl, A.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Viruses
Publisher:MDPI
ISSN:1999-4915
ISSN (Online):1999-4915
Published Online:11 July 2020
Copyright Holders:Copyright © 2020 The Authors
First Published:First published in Viruses 12(7): 748
Publisher Policy:Reproduced under a Creative Commons License

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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
171895MAPPAlain KohlEuropean Commission (EC)661232III-MRC-GU Centre for Virus Research
174030DOST-Newton PhD ScholarshipAlain KohlBritish Council (UK) (BRCOU-UK)279705176III-MRC-GU Centre for Virus Research