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aBravo Is a Novel Aedes aegypti Antiviral Protein That Interacts with, but Acts Independently of, the Exogenous siRNA Pathway Effector Dicer 2

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 dou...

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Autores principales: Varjak, Margus, Gestuveo, Rommel J., Burchmore, Richard, Schnettler, Esther, Kohl, Alain
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7411624/
https://www.ncbi.nlm.nih.gov/pubmed/32664591
http://dx.doi.org/10.3390/v12070748
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author Varjak, Margus
Gestuveo, Rommel J.
Burchmore, Richard
Schnettler, Esther
Kohl, Alain
author_facet Varjak, Margus
Gestuveo, Rommel J.
Burchmore, Richard
Schnettler, Esther
Kohl, Alain
author_sort Varjak, Margus
collection PubMed
description 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.
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spelling pubmed-74116242020-08-17 aBravo Is a Novel Aedes aegypti Antiviral Protein That Interacts with, but Acts Independently of, the Exogenous siRNA Pathway Effector Dicer 2 Varjak, Margus Gestuveo, Rommel J. Burchmore, Richard Schnettler, Esther Kohl, Alain Viruses Article 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. MDPI 2020-07-11 /pmc/articles/PMC7411624/ /pubmed/32664591 http://dx.doi.org/10.3390/v12070748 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Varjak, Margus
Gestuveo, Rommel J.
Burchmore, Richard
Schnettler, Esther
Kohl, Alain
aBravo Is a Novel Aedes aegypti Antiviral Protein That Interacts with, but Acts Independently of, the Exogenous siRNA Pathway Effector Dicer 2
title aBravo Is a Novel Aedes aegypti Antiviral Protein That Interacts with, but Acts Independently of, the Exogenous siRNA Pathway Effector Dicer 2
title_full aBravo Is a Novel Aedes aegypti Antiviral Protein That Interacts with, but Acts Independently of, the Exogenous siRNA Pathway Effector Dicer 2
title_fullStr aBravo Is a Novel Aedes aegypti Antiviral Protein That Interacts with, but Acts Independently of, the Exogenous siRNA Pathway Effector Dicer 2
title_full_unstemmed aBravo Is a Novel Aedes aegypti Antiviral Protein That Interacts with, but Acts Independently of, the Exogenous siRNA Pathway Effector Dicer 2
title_short aBravo Is a Novel Aedes aegypti Antiviral Protein That Interacts with, but Acts Independently of, the Exogenous siRNA Pathway Effector Dicer 2
title_sort abravo is a novel aedes aegypti antiviral protein that interacts with, but acts independently of, the exogenous sirna pathway effector dicer 2
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7411624/
https://www.ncbi.nlm.nih.gov/pubmed/32664591
http://dx.doi.org/10.3390/v12070748
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