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Host microRNA interactions with the SARS-CoV-2 viral genome 3’-untranslated region
The 2019 pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has marked the spread of a novel human coronavirus. While the viral life cycle is well understood, most of the interactions at the virus-host interface remain elusive. Furthermore, the molecular mechanisms...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cold Spring Harbor Laboratory
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10245713/ https://www.ncbi.nlm.nih.gov/pubmed/37292986 http://dx.doi.org/10.1101/2023.05.18.541401 |
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author | Frye, Caleb J. Cunningham, Caylee L. Mihailescu, Mihaela Rita |
author_facet | Frye, Caleb J. Cunningham, Caylee L. Mihailescu, Mihaela Rita |
author_sort | Frye, Caleb J. |
collection | PubMed |
description | The 2019 pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has marked the spread of a novel human coronavirus. While the viral life cycle is well understood, most of the interactions at the virus-host interface remain elusive. Furthermore, the molecular mechanisms behind disease severity and immune evasion are still largely unknown. Conserved elements of the viral genome such as secondary structures within the 5’- and 3’-untranslated regions (UTRs) serve as attractive targets of interest and could prove crucial in furthering our understanding of virus-host interactions. It has been proposed that microRNA (miR) interactions with viral components could be used by both the virus and host for their own benefit. Analysis of the SARS-CoV-2 viral genome 3’-UTR has revealed the potential for host cellular miR binding sites, providing sites for specific interactions with the virus. In this study, we demonstrate that the SARS-CoV-2 genome 3’-UTR binds the host cellular miRNAs miR-760-3p, miR-34a-5p, and miR-34b-5p, which have been shown to influence translation of interleukin-6 (IL-6), the IL-6 receptor (IL-6R), as well as progranulin (PGRN), respectively, proteins that have roles in the host immune response and inflammatory pathways. Furthermore, recent work suggests the potential of miR-34a-5p and miR-34b-5p to target and inhibit translation of viral proteins. Native gel electrophoresis and steady-state fluorescence spectroscopy were utilized to characterize the binding of these miRs to their predicted sites within the SARS-CoV-2 genome 3’-UTR. Additionally, we investigated 2’-fluoro-D-arabinonucleic acid (FANA) analogs of these miRNAs as competitive binding inhibitors for these miR binding interactions. The mechanisms detailed in this study have the potential to drive the development of antiviral treatments for SARS-CoV-2 infection, and provide a potential molecular basis for cytokine release syndrome and immune evasion which could implicate the host-virus interface. |
format | Online Article Text |
id | pubmed-10245713 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Cold Spring Harbor Laboratory |
record_format | MEDLINE/PubMed |
spelling | pubmed-102457132023-06-08 Host microRNA interactions with the SARS-CoV-2 viral genome 3’-untranslated region Frye, Caleb J. Cunningham, Caylee L. Mihailescu, Mihaela Rita bioRxiv Article The 2019 pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has marked the spread of a novel human coronavirus. While the viral life cycle is well understood, most of the interactions at the virus-host interface remain elusive. Furthermore, the molecular mechanisms behind disease severity and immune evasion are still largely unknown. Conserved elements of the viral genome such as secondary structures within the 5’- and 3’-untranslated regions (UTRs) serve as attractive targets of interest and could prove crucial in furthering our understanding of virus-host interactions. It has been proposed that microRNA (miR) interactions with viral components could be used by both the virus and host for their own benefit. Analysis of the SARS-CoV-2 viral genome 3’-UTR has revealed the potential for host cellular miR binding sites, providing sites for specific interactions with the virus. In this study, we demonstrate that the SARS-CoV-2 genome 3’-UTR binds the host cellular miRNAs miR-760-3p, miR-34a-5p, and miR-34b-5p, which have been shown to influence translation of interleukin-6 (IL-6), the IL-6 receptor (IL-6R), as well as progranulin (PGRN), respectively, proteins that have roles in the host immune response and inflammatory pathways. Furthermore, recent work suggests the potential of miR-34a-5p and miR-34b-5p to target and inhibit translation of viral proteins. Native gel electrophoresis and steady-state fluorescence spectroscopy were utilized to characterize the binding of these miRs to their predicted sites within the SARS-CoV-2 genome 3’-UTR. Additionally, we investigated 2’-fluoro-D-arabinonucleic acid (FANA) analogs of these miRNAs as competitive binding inhibitors for these miR binding interactions. The mechanisms detailed in this study have the potential to drive the development of antiviral treatments for SARS-CoV-2 infection, and provide a potential molecular basis for cytokine release syndrome and immune evasion which could implicate the host-virus interface. Cold Spring Harbor Laboratory 2023-05-19 /pmc/articles/PMC10245713/ /pubmed/37292986 http://dx.doi.org/10.1101/2023.05.18.541401 Text en https://creativecommons.org/licenses/by/4.0/This work is licensed under a Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/) , which allows reusers to distribute, remix, adapt, and build upon the material in any medium or format, so long as attribution is given to the creator. The license allows for commercial use. |
spellingShingle | Article Frye, Caleb J. Cunningham, Caylee L. Mihailescu, Mihaela Rita Host microRNA interactions with the SARS-CoV-2 viral genome 3’-untranslated region |
title | Host microRNA interactions with the SARS-CoV-2 viral genome 3’-untranslated region |
title_full | Host microRNA interactions with the SARS-CoV-2 viral genome 3’-untranslated region |
title_fullStr | Host microRNA interactions with the SARS-CoV-2 viral genome 3’-untranslated region |
title_full_unstemmed | Host microRNA interactions with the SARS-CoV-2 viral genome 3’-untranslated region |
title_short | Host microRNA interactions with the SARS-CoV-2 viral genome 3’-untranslated region |
title_sort | host microrna interactions with the sars-cov-2 viral genome 3’-untranslated region |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10245713/ https://www.ncbi.nlm.nih.gov/pubmed/37292986 http://dx.doi.org/10.1101/2023.05.18.541401 |
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