RT Journal Article SR Electronic T1 Experimental and mathematical insights on the interactions between poliovirus and a defective interfering genome JF bioRxiv FD Cold Spring Harbor Laboratory SP 2021.01.11.426198 DO 10.1101/2021.01.11.426198 A1 Yuta Shirogane A1 Elsa Rousseau A1 Jakub Voznica A1 Yinghong Xiao A1 Weiheng Su A1 Adam Catching A1 Zachary J. Whitfield A1 Igor M. Rouzine A1 Simone Bianco A1 Raul Andino YR 2021 UL http://biorxiv.org/content/early/2021/01/11/2021.01.11.426198.abstract AB 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. We experimentally determined virus and DI replication during co-infection, and use these data to infer model parameters. Our model predicts, and our experimental measurements confirm, that DI replication and encapsidation are the most important determinants for the outcome of the competition. WT replication inversely correlates with DI replication. Our model predicts that genome replication and effective DI genome encapsidation are critical to effectively inhibit WT production, but an equilibrium can be established which enables WT to replicate, albeit to reduce levels.