PMID (identifiant
de la référence Pubmed) : |
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 (22110627) |
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| Titre : |
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A novel ribozyme-based prophylaxis inhibits influenza A virus replication and protects from severe disease. |
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| Auteur(s) : |
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Julie Motard1, Ronan Rouxel2, Alexandra Paun1, Veronika Von Messling2, Martin Bisaillon ( ) 1, Jean-Pierre Perreault () 1 |
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| Laboratoire : |
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| Résumé : |
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Influenza A virus seasonal outbreaks and occasional pandemics represent a global health threat. The high genetic instability of this virus permits rapid escape from the host immune system and emergence of resistance to antivirals. There is thus an urgent need to develop novel approaches for efficient treatment of newly emerging strains. Based on a sequence alignment of representatives from every subtype known to infect humans, we identified nucleic acid regions that are conserved amongst these influenza A populations. We then engineered SOFA-HDV-Ribozymes as therapeutic tools recognizing these conserved regions to catalytically cleave the corresponding viral mRNA targets. The most promising ribozymes were chosen based on an initial in silico screening, and their efficacy was assessed using in vitro cleavage assays. Further characterization of their antiviral effect in cell culture and in mice led to the gradual identification of prophylactic SOFA-HDV-Ribozyme combinations, providing proof-of-principle for the potential of this novel strategy to develop antivirals against genetically highly variable viruses. |
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| Domaine : |
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Langue du texte
intégral : |
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Anglais |
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1932-6203 |
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| Type de publication : |
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Articles dans des revues avec comité de lecture |
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| DOI : |
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10.1371/journal.pone.0027327 |
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| Journal : |
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| PLoS ONE |
| Publisher |
Public Library of Science |
| ISSN |
1932-6203 |
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| Audience : |
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internationale |
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| Date de publication : |
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2011 |
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Date de publication
électronique : |
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14/11/2011 |
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| Volume : |
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6 |
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| Numéro : |
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11 |
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| Page, identifiant, ... : |
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e27327 |
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| Descripteur(s) MeSH : |
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Animals – Antiviral Agents – Base Sequence – Biocatalysis – Female – HEK293 Cells – Hepatitis Delta Virus – Humans – Influenza A Virus – H1N1 Subtype – Influenza – Human – Mice – Nucleoproteins – RNA – Catalytic – Messenger – Viral – Recombinant Proteins – Virus Replication |
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| Contrat, financement : |
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This work was supported by a grant from the Canadian Institutes of Health Research (CIHR; grant number PAP-99021) to Dr. Bisaillon, Dr. Perreault and Dr. von Messling. The RNA group is also supported by grants from both the Université de Sherbrooke and CIHR (Resource program). Dr. Perreault holds the Canada Research Chair in Genomics and Catalytic RNA. Dr. Motard is a Chercheur Boursier Junior 2 from the Fonds de recherche en santé du Québec. Dr. Bisaillon and Dr. Perreault are members of the Centre de Recherche Clinique Etienne-Lebel. |
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