Back to Search Start Over

Single-Stranded Oligonucleotide-mediated Inhibition of Respiratory Syncytial Virus Infection

Authors :
Axberg Palsson, Sandra
Dondalska, Aleksandra
Bergenstrahle, Joseph A.
Rolfes, Caroline
Bjork, Albin
Sedano, Laura
Power, Ultan
Remeix-Welti, Marie-Anne
Mastrangelo, Peter
Eleouet, Jean-Francois
Le Goffic, Ronan
Galloux, Marie
Spetz, Anna-Lena
Source :
Axberg Palsson, S, Dondalska, A, Bergenstrahle, J A, Rolfes, C, Bjork, A, Sedano, L, Power, U, Remeix-Welti, M-A, Mastrangelo, P, Eleouet, J-F, Le Goffic, R, Galloux, M & Spetz, A-L 2020, ' Single-Stranded Oligonucleotide-mediated Inhibition of Respiratory Syncytial Virus Infection ', Frontiers in immunology, vol. 11, 580547 . https://doi.org/10.3389/fimmu.2020.580547
Publication Year :
2020

Abstract

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 additionallyresults in the upregulation of ISGs.

Details

Language :
English
Database :
OpenAIRE
Journal :
Axberg Palsson, S, Dondalska, A, Bergenstrahle, J A, Rolfes, C, Bjork, A, Sedano, L, Power, U, Remeix-Welti, M-A, Mastrangelo, P, Eleouet, J-F, Le Goffic, R, Galloux, M & Spetz, A-L 2020, ' Single-Stranded Oligonucleotide-mediated Inhibition of Respiratory Syncytial Virus Infection ', Frontiers in immunology, vol. 11, 580547 . https://doi.org/10.3389/fimmu.2020.580547
Accession number :
edsair.od......2607..8f325514c39f8fb71c3e4beb6a976c2e
Full Text :
https://doi.org/10.3389/fimmu.2020.580547