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Spatio-temporal modelling of in vitro viral infection: the impact of defective interfering particles on type I interferon response

Li, Y.; Nielsen, B. F.; Levin, S. A.; te Velthuis, A. J. W.; Grenfell, B.

2025-11-28 systems biology
10.1101/2025.10.09.681519 bioRxiv
Show abstract

Defective interfering particles (DIPs) are incomplete viral genomes that modulate infection by competing with wild-type viruses and activating innate immunity. How DIPs interact with type I interferon (IFN) in spatially structured environments remains unclear. Focusing initially on influenza A, we developed a spatially explicit, stochastic model of in vitro viral infection integrating virus and DIP replication, IFN signalling, and alternative dispersal modes. We find that: (1) our model captures the ring-like and patchy plaque morphologies observed experimentally; (2) IFN production peaks at an intermediate DIP ratio, reflecting a trade-off between early immune activation and sufficient co-infection; and (3) even a small fraction of long-range spread of virus and DIPs escape containment despite longer IFN ranges; this causes stronger antiviral responses but earlier peaks in lysis at similar levels of cell loss. The model is available as an interactive platform: https://shiny-spatial-infection-app-production.up.railway.app/.

Published in PLOS Computational Biology (predicted rank #1) · training set

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