Defective Viral Genomes Reveal History-dependent Self-regulation of Type I Interferon Dynamics

A Bayesian model of influenza infection shows that host cells’ cumulative Type I interferon exposure, not instantaneous IFN level, shapes subsequent IFN induction under DVG-driven feedback.

• Why it matters: IFN must both rise to control viruses and then decline to prevent dysregulation, yet DVGs’ role in tuning this negative feedback is unclear during highly immunogenic infections.
• What they did: The authors combined in vitro dose-response experiments using viral RNA with exogenous IFN and an in vivo Bayesian computational model incorporating DVG–virus competition and positive/negative IFN feedback, then calibrated it to published influenza data.
• The result: The model predicts DVGs can both trigger IFN and lower it via negative feedback, explaining declining IFN despite rising virus/DVGs and local suppression of innate responses in neighboring uninfected cells.

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