Mathematical model calibrated to in vitro data predicts mechanisms of antiviral action of the influenza defective interfering particle "OP7"

Daniel Rüdiger; Julita Piasecka; Jan Küchler; Carolina Pontes; Tanja Laske; Sascha Y Kupke; Udo Reichl

doi:10.1016/j.isci.2024.109421

Mathematical model calibrated to in vitro data predicts mechanisms of antiviral action of the influenza defective interfering particle "OP7"

iScience. 2024 Mar 5;27(4):109421. doi: 10.1016/j.isci.2024.109421. eCollection 2024 Apr 19.

Authors

Daniel Rüdiger¹, Julita Piasecka¹, Jan Küchler¹, Carolina Pontes¹, Tanja Laske^{1

2}, Sascha Y Kupke¹, Udo Reichl^{1

3}

Affiliations

¹ Department of Bioprocess Engineering, Max Planck Institute for Dynamics of Complex Technical Systems, 39106 Magdeburg, Saxony-Anhalt, Germany.
² Institute for Computational Systems Biology, University of Hamburg, 20148 Hamburg, Germany.
³ Chair of Bioprocess Engineering, Otto-von-Guericke University, 39106 Magdeburg, Saxony-Anhalt, Germany.

Abstract

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.

Keywords: Biological sciences; Biological sciences research methodologies; Natural sciences.