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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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2024-02-01
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| Series: | PLoS Computational Biology |
| Online Access: | https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1011373&type=printable |
| _version_ | 1797296222413783040 |
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| author | Connor R King Casey-Tyler Berezin Jean Peccoud |
| author_facet | Connor R King Casey-Tyler Berezin Jean Peccoud |
| author_sort | Connor R King |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-07T22:00:17Z |
| format | Article |
| id | doaj.art-9e0b59e460b94dcdb2a99f8b1a1b3f57 |
| institution | Directory Open Access Journal |
| issn | 1553-734X 1553-7358 |
| language | English |
| last_indexed | 2024-03-07T22:00:17Z |
| publishDate | 2024-02-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Computational Biology |
| spelling | doaj.art-9e0b59e460b94dcdb2a99f8b1a1b3f572024-02-24T05:31:21ZengPublic Library of Science (PLoS)PLoS Computational Biology1553-734X1553-73582024-02-01202e101137310.1371/journal.pcbi.1011373Stochastic model of vesicular stomatitis virus replication reveals mutational effects on virion production.Connor R KingCasey-Tyler BerezinJean PeccoudWe 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.https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1011373&type=printable |
| spellingShingle | Connor R King Casey-Tyler Berezin Jean Peccoud Stochastic model of vesicular stomatitis virus replication reveals mutational effects on virion production. PLoS Computational Biology |
| title | Stochastic model of vesicular stomatitis virus replication reveals mutational effects on virion production. |
| title_full | Stochastic model of vesicular stomatitis virus replication reveals mutational effects on virion production. |
| title_fullStr | Stochastic model of vesicular stomatitis virus replication reveals mutational effects on virion production. |
| title_full_unstemmed | Stochastic model of vesicular stomatitis virus replication reveals mutational effects on virion production. |
| title_short | Stochastic model of vesicular stomatitis virus replication reveals mutational effects on virion production. |
| title_sort | stochastic model of vesicular stomatitis virus replication reveals mutational effects on virion production |
| url | https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1011373&type=printable |
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