A novel ribozyme-based prophylaxis inhibits influenza A virus replication and protects from severe disease.
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 efficien...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2011-01-01
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| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0027327&type=printable |
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| author | Julie Motard Ronan Rouxel Alexandra Paun Veronika von Messling Martin Bisaillon Jean-Pierre Perreault |
| author_facet | Julie Motard Ronan Rouxel Alexandra Paun Veronika von Messling Martin Bisaillon Jean-Pierre Perreault |
| author_sort | Julie Motard |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-4bfdc9cb97464ac2b6859e7d44e0081d |
| institution | Kabale University |
| issn | 1932-6203 |
| language | English |
| publishDate | 2011-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-4bfdc9cb97464ac2b6859e7d44e0081d2025-08-20T03:25:08ZengPublic Library of Science (PLoS)PLoS ONE1932-62032011-01-01611e2732710.1371/journal.pone.0027327A novel ribozyme-based prophylaxis inhibits influenza A virus replication and protects from severe disease.Julie MotardRonan RouxelAlexandra PaunVeronika von MesslingMartin BisaillonJean-Pierre PerreaultInfluenza 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.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0027327&type=printable |
| spellingShingle | Julie Motard Ronan Rouxel Alexandra Paun Veronika von Messling Martin Bisaillon Jean-Pierre Perreault A novel ribozyme-based prophylaxis inhibits influenza A virus replication and protects from severe disease. PLoS ONE |
| title | A novel ribozyme-based prophylaxis inhibits influenza A virus replication and protects from severe disease. |
| title_full | A novel ribozyme-based prophylaxis inhibits influenza A virus replication and protects from severe disease. |
| title_fullStr | A novel ribozyme-based prophylaxis inhibits influenza A virus replication and protects from severe disease. |
| title_full_unstemmed | A novel ribozyme-based prophylaxis inhibits influenza A virus replication and protects from severe disease. |
| title_short | A novel ribozyme-based prophylaxis inhibits influenza A virus replication and protects from severe disease. |
| title_sort | novel ribozyme based prophylaxis inhibits influenza a virus replication and protects from severe disease |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0027327&type=printable |
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