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

Yuta Shirogane,Simone Bianco,Yinghong Xiao,Adam Catching,Weiheng Su,Igor M Rouzine,Raul Andino,Elsa Rousseau,Jakub Voznica,Zachary J Whitfield

doi:10.1371/journal.ppat.1009277

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.

Highlights

Co-infections, the simultaneous infection of a host by multiple pathogen species, are frequently observed [1, 2]
We examined the competition between poliovirus WT and defective interfering (DI) genomes within cells during one infection cycle, using a coarse grained dynamic model
WT poliovirus and DI genomic RNAs were transfected by electroporation to HeLaS3 cells and infectious titers of WT virus were determined over time by plaque assay

Summary

Introduction

Co-infections, the simultaneous infection of a host by multiple pathogen species, are frequently observed [1, 2]. The interactions between these microrganisms can determine the trajectories and outcomes of infection. Exploitation competition is a passive process in which pathogens compete for access to host resources. Apparent competition occurs when the a population increases in the number of individuals. This, in turn, results in the increase in number of predators. In the context of the ecology of infection, apparent competition is associated with the stimulation of host immune responses, which acts as predator [3]. Interference competition represents a direct attack inhibiting the growth, reproduction or transmission of competitors, either chemically or mechanically [5]

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