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Control of RNA viruses in mosquito cells through the acquisition of vDNA and endogenous viral elements

Aedes aegypti transmit pathogenic arboviruses while the mosquito itself tolerates the infection. We examine a piRNA-based immunity that relies on the acquisition of viral derived cDNA (vDNA) and how this pathway discriminates between self and non-self. The piRNAs derived from these vDNAs are essenti...

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Autores principales: Tassetto, Michel, Kunitomi, Mark, Whitfield, Zachary J, Dolan, Patrick T, Sánchez-Vargas, Irma, Garcia-Knight, Miguel, Ribiero, Isabel, Chen, Taotao, Olson, Ken E, Andino, Raul
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6797480/
https://www.ncbi.nlm.nih.gov/pubmed/31621580
http://dx.doi.org/10.7554/eLife.41244
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author Tassetto, Michel
Kunitomi, Mark
Whitfield, Zachary J
Dolan, Patrick T
Sánchez-Vargas, Irma
Garcia-Knight, Miguel
Ribiero, Isabel
Chen, Taotao
Olson, Ken E
Andino, Raul
author_facet Tassetto, Michel
Kunitomi, Mark
Whitfield, Zachary J
Dolan, Patrick T
Sánchez-Vargas, Irma
Garcia-Knight, Miguel
Ribiero, Isabel
Chen, Taotao
Olson, Ken E
Andino, Raul
author_sort Tassetto, Michel
collection PubMed
description Aedes aegypti transmit pathogenic arboviruses while the mosquito itself tolerates the infection. We examine a piRNA-based immunity that relies on the acquisition of viral derived cDNA (vDNA) and how this pathway discriminates between self and non-self. The piRNAs derived from these vDNAs are essential for virus control and Piwi4 has a central role in the pathway. Piwi4 binds preferentially to virus-derived piRNAs but not to transposon-targeting piRNAs. Analysis of episomal vDNA from infected cells reveals that vDNA molecules are acquired through a discriminatory process of reverse-transcription and recombination directed by endogenous retrotransposons. Using a high-resolution Ae. aegypti genomic sequence, we found that vDNAs integrated in the host genome as endogenous viral elements (EVEs), produce antisense piRNAs that are preferentially loaded onto Piwi4. Importantly, EVE-derived piRNAs are specifically loaded onto Piwi4 to inhibit virus replication. Thus, Ae. aegypti employs a sophisticated antiviral mechanism that promotes viral persistence and generates long-lasting adaptive immunity.
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spelling pubmed-67974802019-10-21 Control of RNA viruses in mosquito cells through the acquisition of vDNA and endogenous viral elements Tassetto, Michel Kunitomi, Mark Whitfield, Zachary J Dolan, Patrick T Sánchez-Vargas, Irma Garcia-Knight, Miguel Ribiero, Isabel Chen, Taotao Olson, Ken E Andino, Raul eLife Immunology and Inflammation Aedes aegypti transmit pathogenic arboviruses while the mosquito itself tolerates the infection. We examine a piRNA-based immunity that relies on the acquisition of viral derived cDNA (vDNA) and how this pathway discriminates between self and non-self. The piRNAs derived from these vDNAs are essential for virus control and Piwi4 has a central role in the pathway. Piwi4 binds preferentially to virus-derived piRNAs but not to transposon-targeting piRNAs. Analysis of episomal vDNA from infected cells reveals that vDNA molecules are acquired through a discriminatory process of reverse-transcription and recombination directed by endogenous retrotransposons. Using a high-resolution Ae. aegypti genomic sequence, we found that vDNAs integrated in the host genome as endogenous viral elements (EVEs), produce antisense piRNAs that are preferentially loaded onto Piwi4. Importantly, EVE-derived piRNAs are specifically loaded onto Piwi4 to inhibit virus replication. Thus, Ae. aegypti employs a sophisticated antiviral mechanism that promotes viral persistence and generates long-lasting adaptive immunity. eLife Sciences Publications, Ltd 2019-10-17 /pmc/articles/PMC6797480/ /pubmed/31621580 http://dx.doi.org/10.7554/eLife.41244 Text en © 2019, Tassetto et al http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Immunology and Inflammation
Tassetto, Michel
Kunitomi, Mark
Whitfield, Zachary J
Dolan, Patrick T
Sánchez-Vargas, Irma
Garcia-Knight, Miguel
Ribiero, Isabel
Chen, Taotao
Olson, Ken E
Andino, Raul
Control of RNA viruses in mosquito cells through the acquisition of vDNA and endogenous viral elements
title Control of RNA viruses in mosquito cells through the acquisition of vDNA and endogenous viral elements
title_full Control of RNA viruses in mosquito cells through the acquisition of vDNA and endogenous viral elements
title_fullStr Control of RNA viruses in mosquito cells through the acquisition of vDNA and endogenous viral elements
title_full_unstemmed Control of RNA viruses in mosquito cells through the acquisition of vDNA and endogenous viral elements
title_short Control of RNA viruses in mosquito cells through the acquisition of vDNA and endogenous viral elements
title_sort control of rna viruses in mosquito cells through the acquisition of vdna and endogenous viral elements
topic Immunology and Inflammation
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6797480/
https://www.ncbi.nlm.nih.gov/pubmed/31621580
http://dx.doi.org/10.7554/eLife.41244
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