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Single-stranded DNA aptamer that specifically binds to the influenza virus NS1 protein suppresses interferon antagonism.
- Source :
-
Antiviral research [Antiviral Res] 2013 Nov; Vol. 100 (2), pp. 337-45. Date of Electronic Publication: 2013 Sep 19. - Publication Year :
- 2013
-
Abstract
- Non-structural protein 1 (NS1) of the influenza A virus (IAV) inhibits the host's innate immune response by suppressing the induction of interferons (IFNs). Therefore, blocking NS1 activity can be a potential strategy in the development of antiviral agents against IAV infection. In the present study, we selected a single-stranded DNA aptamer specific to the IAV NS1 protein after 15 cycles of systematic evolution of ligands by exponential enrichment (SELEX) procedure and examined the ability of the selected aptamer to inhibit the function of NS1. The selected aptamer binds to NS1 with a Kd of 18.91±3.95nM and RNA binding domain of NS1 is determined to be critical for the aptamer binding. The aptamer has a G-rich sequence in the random sequence region and forms a G-quadruplex structure. The localization of the aptamer bound to NS1 in cells was determined by confocal images, and flow cytometry analysis further demonstrated that the selected aptamer binds specifically to NS1. In addition, luciferase reporter gene assay, quantitative RT-PCR, and enzyme-linked immunosorbent assay (ELISA) experiments demonstrated that the selected aptamer had the ability to induce IFN-β by suppressing the function of NS1. Importantly, we also found that the selected aptamer was able to inhibit the viral replication without affecting cell viability. These results indicate that the selected ssDNA aptamer has strong potential to be further developed as a therapeutic agent against IAV.<br /> (Copyright © 2013 Elsevier B.V. All rights reserved.)
- Subjects :
- Animals
Antiviral Agents isolation & purification
Aptamers, Nucleotide isolation & purification
Cell Line
Cell Survival drug effects
DNA, Single-Stranded isolation & purification
Humans
Influenza A virus immunology
Influenza A virus physiology
Interferons immunology
Kinetics
Mice
Protein Binding
SELEX Aptamer Technique
Virus Replication drug effects
Antiviral Agents metabolism
Aptamers, Nucleotide metabolism
DNA, Single-Stranded metabolism
Influenza A virus drug effects
Interferons biosynthesis
Viral Nonstructural Proteins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1872-9096
- Volume :
- 100
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Antiviral research
- Publication Type :
- Academic Journal
- Accession number :
- 24055449
- Full Text :
- https://doi.org/10.1016/j.antiviral.2013.09.004