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

Author:

Shirogane YutaORCID,Rousseau ElsaORCID,Voznica JakubORCID,Xiao Yinghong,Su Weiheng,Catching AdamORCID,Whitfield Zachary J.,Rouzine Igor M.,Bianco Simone,Andino RaulORCID

Abstract

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 enables exploring the parameter space of the WT and DI competition. We also experimentally examined virus and DI replication kinetics during co-infection, and used these data to infer model parameters. Our model identifies, and our experimental measurements confirm, that the efficiencies 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.

Funder

Defense Advanced Research Projects Agency

Agence National de Recherche, France

Publisher

Public Library of Science (PLoS)

Subject

Virology,Genetics,Molecular Biology,Immunology,Microbiology,Parasitology

Reference76 articles.

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