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Targeting of genomic and negative‐sense strands of viral RNA contributes to antiviral resistance mediated by artificial miRNAs and promotes the emergence of complex viral populations

Technology based on artificial small RNAs, including artificial microRNAs (amiRNAs), exploits natural RNA silencing mechanisms to achieve silencing of endogenous genes or pathogens. This technology has been successfully employed to generate resistance against different eukaryotic viruses. However, i...

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Autores principales: Mesel, Frida, Zhao, Mingmin, García, Beatriz, Simón‐Mateo, Carmen, García, Juan Antonio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9562735/
https://www.ncbi.nlm.nih.gov/pubmed/35989243
http://dx.doi.org/10.1111/mpp.13258
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author Mesel, Frida
Zhao, Mingmin
García, Beatriz
Simón‐Mateo, Carmen
García, Juan Antonio
author_facet Mesel, Frida
Zhao, Mingmin
García, Beatriz
Simón‐Mateo, Carmen
García, Juan Antonio
author_sort Mesel, Frida
collection PubMed
description Technology based on artificial small RNAs, including artificial microRNAs (amiRNAs), exploits natural RNA silencing mechanisms to achieve silencing of endogenous genes or pathogens. This technology has been successfully employed to generate resistance against different eukaryotic viruses. However, information about viral RNA molecules effectively targeted by these small RNAs is rather conflicting, and factors contributing to the selection of virus mutants escaping the antiviral activity of virus‐specific small RNAs have not been studied in detail. In this work, we transformed Nicotiana benthamiana plants with amiRNA constructs designed against the potyvirus plum pox virus (PPV), a positive‐sense RNA virus, and obtained lines highly resistant to PPV infection and others showing partial resistance. These lines have allowed us to verify that amiRNA directed against genomic RNA is more efficient than amiRNA targeting its complementary strand. However, we also provide evidence that the negative‐sense RNA strand is cleaved by the amiRNA‐guided RNA silencing machinery. Our results show that the selection pressure posed by the amiRNA action on both viral RNA strands causes an evolutionary explosion that results in the emergence of a broad range of virus variants, which can further expand in the presence, and even in the absence, of antiviral challenges.
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spelling pubmed-95627352022-10-16 Targeting of genomic and negative‐sense strands of viral RNA contributes to antiviral resistance mediated by artificial miRNAs and promotes the emergence of complex viral populations Mesel, Frida Zhao, Mingmin García, Beatriz Simón‐Mateo, Carmen García, Juan Antonio Mol Plant Pathol Original Articles Technology based on artificial small RNAs, including artificial microRNAs (amiRNAs), exploits natural RNA silencing mechanisms to achieve silencing of endogenous genes or pathogens. This technology has been successfully employed to generate resistance against different eukaryotic viruses. However, information about viral RNA molecules effectively targeted by these small RNAs is rather conflicting, and factors contributing to the selection of virus mutants escaping the antiviral activity of virus‐specific small RNAs have not been studied in detail. In this work, we transformed Nicotiana benthamiana plants with amiRNA constructs designed against the potyvirus plum pox virus (PPV), a positive‐sense RNA virus, and obtained lines highly resistant to PPV infection and others showing partial resistance. These lines have allowed us to verify that amiRNA directed against genomic RNA is more efficient than amiRNA targeting its complementary strand. However, we also provide evidence that the negative‐sense RNA strand is cleaved by the amiRNA‐guided RNA silencing machinery. Our results show that the selection pressure posed by the amiRNA action on both viral RNA strands causes an evolutionary explosion that results in the emergence of a broad range of virus variants, which can further expand in the presence, and even in the absence, of antiviral challenges. John Wiley and Sons Inc. 2022-08-21 /pmc/articles/PMC9562735/ /pubmed/35989243 http://dx.doi.org/10.1111/mpp.13258 Text en © 2022 The Authors. Molecular Plant Pathology published by British Society for Plant Pathology and John Wiley & Sons Ltd. https://creativecommons.org/licenses/by-nc/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
spellingShingle Original Articles
Mesel, Frida
Zhao, Mingmin
García, Beatriz
Simón‐Mateo, Carmen
García, Juan Antonio
Targeting of genomic and negative‐sense strands of viral RNA contributes to antiviral resistance mediated by artificial miRNAs and promotes the emergence of complex viral populations
title Targeting of genomic and negative‐sense strands of viral RNA contributes to antiviral resistance mediated by artificial miRNAs and promotes the emergence of complex viral populations
title_full Targeting of genomic and negative‐sense strands of viral RNA contributes to antiviral resistance mediated by artificial miRNAs and promotes the emergence of complex viral populations
title_fullStr Targeting of genomic and negative‐sense strands of viral RNA contributes to antiviral resistance mediated by artificial miRNAs and promotes the emergence of complex viral populations
title_full_unstemmed Targeting of genomic and negative‐sense strands of viral RNA contributes to antiviral resistance mediated by artificial miRNAs and promotes the emergence of complex viral populations
title_short Targeting of genomic and negative‐sense strands of viral RNA contributes to antiviral resistance mediated by artificial miRNAs and promotes the emergence of complex viral populations
title_sort targeting of genomic and negative‐sense strands of viral rna contributes to antiviral resistance mediated by artificial mirnas and promotes the emergence of complex viral populations
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9562735/
https://www.ncbi.nlm.nih.gov/pubmed/35989243
http://dx.doi.org/10.1111/mpp.13258
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