Document Type

Article

Publication Date

2-1-2023

Comments

This article is the author's final published version in PeerJ, Volume 11, 2023, Article number e14828.

The published version is available at https://doi.org/10.7717/peerj.14828. Copyright © 2023 Staroverov et al.

Abstract

Mathematical modeling is widely used to study within-host viral dynamics. However, to the best of our knowledge, for the case of SARS-CoV-2 such analyses were mainly conducted with the use of viral load data and for the wild type (WT) variant of the virus. In addition, only few studies analyzed models for in vitro data, which are less noisy and more reproducible. In this work we collected multiple data types for SARS-CoV-2-infected Caco-2 cell lines, including infectious virus titers, measurements of intracellular viral RNA, cell viability data and percentage of infected cells for the WT and Delta variants. We showed that standard models cannot explain some key observations given the absence of cytopathic effect in human cell lines. We propose a novel mathematical model for in vitro SARS-CoV-2 dynamics, which included explicit modeling of intracellular events such as exhaustion of cellular resources required for virus production. The model also explicitly considers innate immune response. The proposed model accurately explained experimental data. Attenuated replication of the Delta variant in Caco-2 cells could be explained by our model on the basis of just two parameters: decreased cell entry rate and increased cytokine production rate.

Creative Commons License

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.

Additional Files
Appendix.pdf (506 kB)

Language

English

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