Aedes aegypti miRNA-33 modulates permethrin induced toxicity by regulating VGSC transcripts

Abstract Aedes aegypti is a major vector of Zika, dengue, and other arboviruses. Permethrin adulticidal spraying, which targets the voltage-gated sodium channel (VGSC), is commonly done to reduce local mosquito populations and protect humans from exposure to arbovirus pathogens transmitted by this d...

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Autores principales:	Tristan D. Kubik, Trey K. Snell, Karla Saavedra-Rodriguez, Jeffrey Wilusz, John R. Anderson, Saul Lozano-Fuentes, William C. Black, Corey L. Campbell
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/c88eaaa839f844e9a669cfc4a4977fae
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spelling	oai:doaj.org-article:c88eaaa839f844e9a669cfc4a4977fae2021-12-02T14:23:18ZAedes aegypti miRNA-33 modulates permethrin induced toxicity by regulating VGSC transcripts10.1038/s41598-021-86665-62045-2322https://doaj.org/article/c88eaaa839f844e9a669cfc4a4977fae2021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-86665-6https://doaj.org/toc/2045-2322Abstract Aedes aegypti is a major vector of Zika, dengue, and other arboviruses. Permethrin adulticidal spraying, which targets the voltage-gated sodium channel (VGSC), is commonly done to reduce local mosquito populations and protect humans from exposure to arbovirus pathogens transmitted by this dangerous pest. Permethrin resistance, however, is a growing problem and understanding its underlying molecular basis may identify avenues to combat it. We identified a single G:C polymorphism in pre-miR-33 that was genetically associated with permethrin resistance; resulting isoforms had structural differences that may affect DICER-1/pre-miRNA processing rates. We then assessed the effects of overexpression of pre-miR-33 isoforms on permethrin toxicological phenotypes, VGSC transcript abundance and protein levels for two genetically related mosquito strains. One strain had its naturally high permethrin resistance levels maintained by periodic treatment, and the other was released from selection. VGSC protein levels were lower in the permethrin resistant strain than in the related permethrin-susceptible strain. Overexpression of the G-pre-miR-33 isoform reduced VGSC expression levels in both strains. To further elucidate changes in gene expression associated with permethrin resistance, exome-capture gDNA deep sequencing, genetic association mapping and subsequent gene set enrichment analysis revealed that transport genes, in particular, were selected in resistant versus susceptible mosquitoes. Collectively, these data indicate that miR-33 regulates VGSC expression as part of a nuanced system of neuronal regulation that contributes to a network of heritable features determining permethrin resistance.Tristan D. KubikTrey K. SnellKarla Saavedra-RodriguezJeffrey WiluszJohn R. AndersonSaul Lozano-FuentesWilliam C. BlackCorey L. CampbellNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Tristan D. Kubik Trey K. Snell Karla Saavedra-Rodriguez Jeffrey Wilusz John R. Anderson Saul Lozano-Fuentes William C. Black Corey L. Campbell Aedes aegypti miRNA-33 modulates permethrin induced toxicity by regulating VGSC transcripts
description	Abstract Aedes aegypti is a major vector of Zika, dengue, and other arboviruses. Permethrin adulticidal spraying, which targets the voltage-gated sodium channel (VGSC), is commonly done to reduce local mosquito populations and protect humans from exposure to arbovirus pathogens transmitted by this dangerous pest. Permethrin resistance, however, is a growing problem and understanding its underlying molecular basis may identify avenues to combat it. We identified a single G:C polymorphism in pre-miR-33 that was genetically associated with permethrin resistance; resulting isoforms had structural differences that may affect DICER-1/pre-miRNA processing rates. We then assessed the effects of overexpression of pre-miR-33 isoforms on permethrin toxicological phenotypes, VGSC transcript abundance and protein levels for two genetically related mosquito strains. One strain had its naturally high permethrin resistance levels maintained by periodic treatment, and the other was released from selection. VGSC protein levels were lower in the permethrin resistant strain than in the related permethrin-susceptible strain. Overexpression of the G-pre-miR-33 isoform reduced VGSC expression levels in both strains. To further elucidate changes in gene expression associated with permethrin resistance, exome-capture gDNA deep sequencing, genetic association mapping and subsequent gene set enrichment analysis revealed that transport genes, in particular, were selected in resistant versus susceptible mosquitoes. Collectively, these data indicate that miR-33 regulates VGSC expression as part of a nuanced system of neuronal regulation that contributes to a network of heritable features determining permethrin resistance.
format	article
author	Tristan D. Kubik Trey K. Snell Karla Saavedra-Rodriguez Jeffrey Wilusz John R. Anderson Saul Lozano-Fuentes William C. Black Corey L. Campbell
author_facet	Tristan D. Kubik Trey K. Snell Karla Saavedra-Rodriguez Jeffrey Wilusz John R. Anderson Saul Lozano-Fuentes William C. Black Corey L. Campbell
author_sort	Tristan D. Kubik
title	Aedes aegypti miRNA-33 modulates permethrin induced toxicity by regulating VGSC transcripts
title_short	Aedes aegypti miRNA-33 modulates permethrin induced toxicity by regulating VGSC transcripts
title_full	Aedes aegypti miRNA-33 modulates permethrin induced toxicity by regulating VGSC transcripts
title_fullStr	Aedes aegypti miRNA-33 modulates permethrin induced toxicity by regulating VGSC transcripts
title_full_unstemmed	Aedes aegypti miRNA-33 modulates permethrin induced toxicity by regulating VGSC transcripts
title_sort	aedes aegypti mirna-33 modulates permethrin induced toxicity by regulating vgsc transcripts
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/c88eaaa839f844e9a669cfc4a4977fae
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Aedes aegypti miRNA-33 modulates permethrin induced toxicity by regulating VGSC transcripts

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