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No G-Quadruplex Structures in the DNA of Parvovirus B19: Experimental Evidence versus Bioinformatic Predictions

Parvovirus B19 (B19V), an ssDNA virus in the family Parvoviridae, is a human pathogenic virus, responsible for a wide range of clinical manifestations, still in need of effective and specific antivirals. DNA structures, including G-quadruplex (G4), have been recognised as relevant functional feature...

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Autores principales: Bua, Gloria, Tedesco, Daniele, Conti, Ilaria, Reggiani, Alessandro, Bartolini, Manuela, Gallinella, Giorgio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7552014/
https://www.ncbi.nlm.nih.gov/pubmed/32854437
http://dx.doi.org/10.3390/v12090935
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author Bua, Gloria
Tedesco, Daniele
Conti, Ilaria
Reggiani, Alessandro
Bartolini, Manuela
Gallinella, Giorgio
author_facet Bua, Gloria
Tedesco, Daniele
Conti, Ilaria
Reggiani, Alessandro
Bartolini, Manuela
Gallinella, Giorgio
author_sort Bua, Gloria
collection PubMed
description Parvovirus B19 (B19V), an ssDNA virus in the family Parvoviridae, is a human pathogenic virus, responsible for a wide range of clinical manifestations, still in need of effective and specific antivirals. DNA structures, including G-quadruplex (G4), have been recognised as relevant functional features in viral genomes, and small-molecule ligands binding to these structures are promising antiviral compounds. Bioinformatic tools predict the presence of potential G4 forming sequences (PQSs) in the genome of B19V, raising interest as targets for antiviral strategies. Predictions locate PQSs in the genomic terminal regions, in proximity to replicative origins. The actual propensity of these PQSs to form G4 structures was investigated by circular dichroism spectroscopic analysis on synthetic oligonucleotides of corresponding sequences. No signature of G4 structures was detected, and the interaction with the G4 ligand BRACO-19 (N,N′-(9-{[4-(dimethylamino)phenyl]amino}acridine-3,6-diyl)bis(3-pyrrolidin-1-ylpropanamide) did not appear consistent with the stabilisation of G4 structures. Any potential role of PQSs in the viral lifecycle was then assessed in an in vitro infection model system, by evaluating any variation in replication or expression of B19V in the presence of the G4 ligands BRACO-19 and pyridostatin. Neither showed a significant inhibitory activity on B19V replication or expression. Experimental challenge did not support bioinformatic predictions. The terminal regions of B19V are characterised by relevant sequence and symmetry constraints, which are functional to viral replication. Our experiments suggest that these impose a stringent requirement prevailing over the propensity of forming actual G4 structures.
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spelling pubmed-75520142020-10-14 No G-Quadruplex Structures in the DNA of Parvovirus B19: Experimental Evidence versus Bioinformatic Predictions Bua, Gloria Tedesco, Daniele Conti, Ilaria Reggiani, Alessandro Bartolini, Manuela Gallinella, Giorgio Viruses Article Parvovirus B19 (B19V), an ssDNA virus in the family Parvoviridae, is a human pathogenic virus, responsible for a wide range of clinical manifestations, still in need of effective and specific antivirals. DNA structures, including G-quadruplex (G4), have been recognised as relevant functional features in viral genomes, and small-molecule ligands binding to these structures are promising antiviral compounds. Bioinformatic tools predict the presence of potential G4 forming sequences (PQSs) in the genome of B19V, raising interest as targets for antiviral strategies. Predictions locate PQSs in the genomic terminal regions, in proximity to replicative origins. The actual propensity of these PQSs to form G4 structures was investigated by circular dichroism spectroscopic analysis on synthetic oligonucleotides of corresponding sequences. No signature of G4 structures was detected, and the interaction with the G4 ligand BRACO-19 (N,N′-(9-{[4-(dimethylamino)phenyl]amino}acridine-3,6-diyl)bis(3-pyrrolidin-1-ylpropanamide) did not appear consistent with the stabilisation of G4 structures. Any potential role of PQSs in the viral lifecycle was then assessed in an in vitro infection model system, by evaluating any variation in replication or expression of B19V in the presence of the G4 ligands BRACO-19 and pyridostatin. Neither showed a significant inhibitory activity on B19V replication or expression. Experimental challenge did not support bioinformatic predictions. The terminal regions of B19V are characterised by relevant sequence and symmetry constraints, which are functional to viral replication. Our experiments suggest that these impose a stringent requirement prevailing over the propensity of forming actual G4 structures. MDPI 2020-08-25 /pmc/articles/PMC7552014/ /pubmed/32854437 http://dx.doi.org/10.3390/v12090935 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Bua, Gloria
Tedesco, Daniele
Conti, Ilaria
Reggiani, Alessandro
Bartolini, Manuela
Gallinella, Giorgio
No G-Quadruplex Structures in the DNA of Parvovirus B19: Experimental Evidence versus Bioinformatic Predictions
title No G-Quadruplex Structures in the DNA of Parvovirus B19: Experimental Evidence versus Bioinformatic Predictions
title_full No G-Quadruplex Structures in the DNA of Parvovirus B19: Experimental Evidence versus Bioinformatic Predictions
title_fullStr No G-Quadruplex Structures in the DNA of Parvovirus B19: Experimental Evidence versus Bioinformatic Predictions
title_full_unstemmed No G-Quadruplex Structures in the DNA of Parvovirus B19: Experimental Evidence versus Bioinformatic Predictions
title_short No G-Quadruplex Structures in the DNA of Parvovirus B19: Experimental Evidence versus Bioinformatic Predictions
title_sort no g-quadruplex structures in the dna of parvovirus b19: experimental evidence versus bioinformatic predictions
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7552014/
https://www.ncbi.nlm.nih.gov/pubmed/32854437
http://dx.doi.org/10.3390/v12090935
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