Mathematical model calibrated to in vitro data predicts mechanisms of antiviral action of the influenza defective interfering particle “OP7”
Summary: Defective interfering particles (DIPs) are regarded as potent broad-spectrum antivirals. We developed a mathematical model that describes intracellular co-infection dynamics of influenza standard virus (STV) and “OP7”, a new type of influenza DIP discovered recently. Based on experimental d...
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| Format: | Article |
| Language: | English |
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Elsevier
2024-04-01
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| Series: | iScience |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004224006424 |
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| author | Daniel Rüdiger Julita Piasecka Jan Küchler Carolina Pontes Tanja Laske Sascha Y. Kupke Udo Reichl |
| author_facet | Daniel Rüdiger Julita Piasecka Jan Küchler Carolina Pontes Tanja Laske Sascha Y. Kupke Udo Reichl |
| author_sort | Daniel Rüdiger |
| collection | DOAJ |
| description | Summary: Defective interfering particles (DIPs) are regarded as potent broad-spectrum antivirals. We developed a mathematical model that describes intracellular co-infection dynamics of influenza standard virus (STV) and “OP7”, a new type of influenza DIP discovered recently. Based on experimental data from in vitro studies to calibrate the model and confirm its predictions, we deduce OP7’s mechanisms of interference, which were yet unknown. Simulations suggest that the “superpromoter” on OP7 genomic viral RNA enhances its replication and results in a depletion of viral proteins. This reduces STV genomic RNA replication, which appears to constitute an antiviral effect. Further, a defective viral protein (M1-OP7) likely causes the deficiency of OP7’s replication. It appears unable to bind to genomic viral RNAs to facilitate their nuclear export, a critical step in the viral life cycle. An improved understanding of OP7’s antiviral mechanism is crucial toward application in humans as a prospective antiviral treatment strategy. |
| first_indexed | 2024-04-24T23:14:22Z |
| format | Article |
| id | doaj.art-f017adf2437f4bf8a8847f4a5920e2df |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-04-24T23:14:22Z |
| publishDate | 2024-04-01 |
| publisher | Elsevier |
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| series | iScience |
| spelling | doaj.art-f017adf2437f4bf8a8847f4a5920e2df2024-03-17T07:58:36ZengElsevieriScience2589-00422024-04-01274109421Mathematical model calibrated to in vitro data predicts mechanisms of antiviral action of the influenza defective interfering particle “OP7”Daniel Rüdiger0Julita Piasecka1Jan Küchler2Carolina Pontes3Tanja Laske4Sascha Y. Kupke5Udo Reichl6Department of Bioprocess Engineering, Max Planck Institute for Dynamics of Complex Technical Systems, 39106 Magdeburg, Saxony-Anhalt, Germany; Corresponding authorDepartment of Bioprocess Engineering, Max Planck Institute for Dynamics of Complex Technical Systems, 39106 Magdeburg, Saxony-Anhalt, GermanyDepartment of Bioprocess Engineering, Max Planck Institute for Dynamics of Complex Technical Systems, 39106 Magdeburg, Saxony-Anhalt, GermanyDepartment of Bioprocess Engineering, Max Planck Institute for Dynamics of Complex Technical Systems, 39106 Magdeburg, Saxony-Anhalt, GermanyDepartment of Bioprocess Engineering, Max Planck Institute for Dynamics of Complex Technical Systems, 39106 Magdeburg, Saxony-Anhalt, Germany; Institute for Computational Systems Biology, University of Hamburg, 20148 Hamburg, GermanyDepartment of Bioprocess Engineering, Max Planck Institute for Dynamics of Complex Technical Systems, 39106 Magdeburg, Saxony-Anhalt, Germany; Corresponding authorDepartment of Bioprocess Engineering, Max Planck Institute for Dynamics of Complex Technical Systems, 39106 Magdeburg, Saxony-Anhalt, Germany; Chair of Bioprocess Engineering, Otto-von-Guericke University, 39106 Magdeburg, Saxony-Anhalt, GermanySummary: Defective interfering particles (DIPs) are regarded as potent broad-spectrum antivirals. We developed a mathematical model that describes intracellular co-infection dynamics of influenza standard virus (STV) and “OP7”, a new type of influenza DIP discovered recently. Based on experimental data from in vitro studies to calibrate the model and confirm its predictions, we deduce OP7’s mechanisms of interference, which were yet unknown. Simulations suggest that the “superpromoter” on OP7 genomic viral RNA enhances its replication and results in a depletion of viral proteins. This reduces STV genomic RNA replication, which appears to constitute an antiviral effect. Further, a defective viral protein (M1-OP7) likely causes the deficiency of OP7’s replication. It appears unable to bind to genomic viral RNAs to facilitate their nuclear export, a critical step in the viral life cycle. An improved understanding of OP7’s antiviral mechanism is crucial toward application in humans as a prospective antiviral treatment strategy.http://www.sciencedirect.com/science/article/pii/S2589004224006424Biological sciencesBiological sciences research methodologiesNatural sciences |
| spellingShingle | Daniel Rüdiger Julita Piasecka Jan Küchler Carolina Pontes Tanja Laske Sascha Y. Kupke Udo Reichl Mathematical model calibrated to in vitro data predicts mechanisms of antiviral action of the influenza defective interfering particle “OP7” iScience Biological sciences Biological sciences research methodologies Natural sciences |
| title | Mathematical model calibrated to in vitro data predicts mechanisms of antiviral action of the influenza defective interfering particle “OP7” |
| title_full | Mathematical model calibrated to in vitro data predicts mechanisms of antiviral action of the influenza defective interfering particle “OP7” |
| title_fullStr | Mathematical model calibrated to in vitro data predicts mechanisms of antiviral action of the influenza defective interfering particle “OP7” |
| title_full_unstemmed | Mathematical model calibrated to in vitro data predicts mechanisms of antiviral action of the influenza defective interfering particle “OP7” |
| title_short | Mathematical model calibrated to in vitro data predicts mechanisms of antiviral action of the influenza defective interfering particle “OP7” |
| title_sort | mathematical model calibrated to in vitro data predicts mechanisms of antiviral action of the influenza defective interfering particle op7 |
| topic | Biological sciences Biological sciences research methodologies Natural sciences |
| url | http://www.sciencedirect.com/science/article/pii/S2589004224006424 |
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