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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Publisher's URL: https://www.mdpi.com/1999-4915/12/7/748
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: | Gestuveo, Dr Rommel and Burchmore, Dr Richard and Schnettler, Dr Esther 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 > School of Infection & Immunity College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research |
| 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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