Stochastic model of vesicular stomatitis virus replication reveals mutational effects on virion production

We present the first complete stochastic model of vesicular stomatitis virus (VSV) intracellular replication. Previous models developed to capture VSV's intracellular replication have either been ODE-based or have not represented the complete replicative cycle, limiting our ability to understan...

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Bibliographic Details
Published in:PLoS computational biology 2024-02, Vol.20 (2), p.e1011373-e1011373
Main Authors: King, Connor R, Berezin, Casey-Tyler, Peccoud, Jean
Format: Article
Language:English
Subjects:
Algorithms
Biology and Life Sciences
Genes
Genomes
Infections
Intracellular
Medicine and Health Sciences
Mutation
Ordinary differential equations
Parameter estimation
Phenotypes
Physical Sciences
Proteins
Replication
Respiratory syncytial virus
Simulation
Stochastic models
Stochasticity
Stomatitis
Virions
Viruses
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Summary:We present the first complete stochastic model of vesicular stomatitis virus (VSV) intracellular replication. Previous models developed to capture VSV's intracellular replication have either been ODE-based or have not represented the complete replicative cycle, limiting our ability to understand the impact of the stochastic nature of early cellular infections on virion production between cells and how these dynamics change in response to mutations. Our model accurately predicts changes in mean virion production in gene-shuffled VSV variants and can capture the distribution of the number of viruses produced. This model has allowed us to enhance our understanding of intercellular variability in virion production, which appears to be influenced by the duration of the early phase of infection, and variation between variants, arising from balancing the time the genome spends in the active state, the speed of incorporating new genomes into virions, and the production of viral components. Being a stochastic model, we can also assess other effects of mutations beyond just the mean number of virions produced, including the probability of aborted infections and the standard deviation of the number of virions produced. Our model provides a biologically interpretable framework for studying the stochastic nature of VSV replication, shedding light on the mechanisms underlying variation in virion production. In the future, this model could enable the design of more complex viral phenotypes when attenuating VSV, moving beyond solely considering the mean number of virions produced.
ISSN:1553-7358
1553-734X
1553-7358
DOI:10.1371/journal.pcbi.1011373