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Single-Stranded Oligonucleotide-Mediated Inhibition of Respiratory Syncytial Virus Infection
Respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory tract infections in young children. Currently, there is no RSV vaccine or universally accessible antiviral treatment available. Addressing the urgent need for new antiviral agents, we have investigated the capacity of...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7752805/ https://www.ncbi.nlm.nih.gov/pubmed/33363532 http://dx.doi.org/10.3389/fimmu.2020.580547 |
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author | Pålsson, Sandra Axberg Dondalska, Aleksandra Bergenstråhle, Joseph Rolfes, Caroline Björk, Albin Sedano, Laura Power, Ultan F. Rameix-Welti, Marie-Anne Lundeberg, Joakim Wahren-Herlenius, Marie Mastrangelo, Peter Eleouet, Jean-Francois Le Goffic, Ronan Galloux, Marie Spetz, Anna-Lena |
author_facet | Pålsson, Sandra Axberg Dondalska, Aleksandra Bergenstråhle, Joseph Rolfes, Caroline Björk, Albin Sedano, Laura Power, Ultan F. Rameix-Welti, Marie-Anne Lundeberg, Joakim Wahren-Herlenius, Marie Mastrangelo, Peter Eleouet, Jean-Francois Le Goffic, Ronan Galloux, Marie Spetz, Anna-Lena |
author_sort | Pålsson, Sandra Axberg |
collection | PubMed |
description | Respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory tract infections in young children. Currently, there is no RSV vaccine or universally accessible antiviral treatment available. Addressing the urgent need for new antiviral agents, we have investigated the capacity of a non-coding single-stranded oligonucleotide (ssON) to inhibit RSV infection. By utilizing a GFP-expressing RSV, we demonstrate that the ssON significantly reduced the proportion of RSV infected A549 cells (lung epithelial cells). Furthermore, we show that ssON’s antiviral activity was length dependent and that both RNA and DNA of this class of oligonucleotides have antiviral activity. We reveal that ssON inhibited RSV infection by competing with the virus for binding to the cellular receptor nucleolin in vitro. Additionally, using a recombinant RSV that expresses luciferase we show that ssON effectively blocked RSV infection in mice. Treatment with ssON in vivo resulted in the upregulation of RSV-induced interferon stimulated genes (ISGs) such as Stat1, Stat2, Cxcl10, and Ccl2. This study highlights the possibility of using oligonucleotides as therapeutic agents against RSV infection. We demonstrate that the mechanism of action of ssON is the inhibition of viral entry in vitro, likely through the binding of the receptor, nucleolin and that ssON treatment against RSV infection in vivo additionally results in the upregulation of ISGs. |
format | Online Article Text |
id | pubmed-7752805 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-77528052020-12-23 Single-Stranded Oligonucleotide-Mediated Inhibition of Respiratory Syncytial Virus Infection Pålsson, Sandra Axberg Dondalska, Aleksandra Bergenstråhle, Joseph Rolfes, Caroline Björk, Albin Sedano, Laura Power, Ultan F. Rameix-Welti, Marie-Anne Lundeberg, Joakim Wahren-Herlenius, Marie Mastrangelo, Peter Eleouet, Jean-Francois Le Goffic, Ronan Galloux, Marie Spetz, Anna-Lena Front Immunol Immunology Respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory tract infections in young children. Currently, there is no RSV vaccine or universally accessible antiviral treatment available. Addressing the urgent need for new antiviral agents, we have investigated the capacity of a non-coding single-stranded oligonucleotide (ssON) to inhibit RSV infection. By utilizing a GFP-expressing RSV, we demonstrate that the ssON significantly reduced the proportion of RSV infected A549 cells (lung epithelial cells). Furthermore, we show that ssON’s antiviral activity was length dependent and that both RNA and DNA of this class of oligonucleotides have antiviral activity. We reveal that ssON inhibited RSV infection by competing with the virus for binding to the cellular receptor nucleolin in vitro. Additionally, using a recombinant RSV that expresses luciferase we show that ssON effectively blocked RSV infection in mice. Treatment with ssON in vivo resulted in the upregulation of RSV-induced interferon stimulated genes (ISGs) such as Stat1, Stat2, Cxcl10, and Ccl2. This study highlights the possibility of using oligonucleotides as therapeutic agents against RSV infection. We demonstrate that the mechanism of action of ssON is the inhibition of viral entry in vitro, likely through the binding of the receptor, nucleolin and that ssON treatment against RSV infection in vivo additionally results in the upregulation of ISGs. Frontiers Media S.A. 2020-12-08 /pmc/articles/PMC7752805/ /pubmed/33363532 http://dx.doi.org/10.3389/fimmu.2020.580547 Text en Copyright © 2020 Pålsson, Dondalska, Bergenstråhle, Rolfes, Björk, Sedano, Power, Rameix-Welti, Lundeberg, Wahren-Herlenius, Mastrangelo, Eleouet, Le Goffic, Galloux and Spetz http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Pålsson, Sandra Axberg Dondalska, Aleksandra Bergenstråhle, Joseph Rolfes, Caroline Björk, Albin Sedano, Laura Power, Ultan F. Rameix-Welti, Marie-Anne Lundeberg, Joakim Wahren-Herlenius, Marie Mastrangelo, Peter Eleouet, Jean-Francois Le Goffic, Ronan Galloux, Marie Spetz, Anna-Lena Single-Stranded Oligonucleotide-Mediated Inhibition of Respiratory Syncytial Virus Infection |
title | Single-Stranded Oligonucleotide-Mediated Inhibition of Respiratory Syncytial Virus Infection |
title_full | Single-Stranded Oligonucleotide-Mediated Inhibition of Respiratory Syncytial Virus Infection |
title_fullStr | Single-Stranded Oligonucleotide-Mediated Inhibition of Respiratory Syncytial Virus Infection |
title_full_unstemmed | Single-Stranded Oligonucleotide-Mediated Inhibition of Respiratory Syncytial Virus Infection |
title_short | Single-Stranded Oligonucleotide-Mediated Inhibition of Respiratory Syncytial Virus Infection |
title_sort | single-stranded oligonucleotide-mediated inhibition of respiratory syncytial virus infection |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7752805/ https://www.ncbi.nlm.nih.gov/pubmed/33363532 http://dx.doi.org/10.3389/fimmu.2020.580547 |
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