Experimental and mathematical insights on the interactions between poliovirus and a defective interfering genome

During replication, RNA viruses accumulate genome alterations, such as mutations and deletions. The interactions between individual variants can determine the fitness of the virus population and, thus, the outcome of infection. To investigate the effects of defective interfering genomes (DI) on wild-type (WT) poliovirus replication, we developed an ordinary differential equation model, which enable exploring the parameter space of the WT and DI competition. We also experimentally examined virus and DI replication kinetics during co-infection, and use these data to infer model parameters. Our model identifies, and our experimental measurements confirm, that the efficiency of DI genome replication and encapsidation are two most critical parameters determining the outcome of WT replication. However, an equilibrium can be established which enables WT to replicate, albeit to reduced levels.

Automated summary

This study investigates the interactions between viruses and defective interfering genomes (DI) during replication using a mathematical model and experimental validation. The efficiency of DI genome replication and encapsidation are identified as critical parameters that determine the outcome of wild-type (WT) virus replication. Despite the establishment of equilibrium, allowing WT virus to replicate, the replication levels are reduced.