Rotavirus-like particle production: Simulation of protein production and particle assembly

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Abstract

In this work we study the production of rotavirus virus-like particles (VLP) using the baculovirus expression vector system (BEVS). A model-based optimization of the infection strategy was performed in order to maximize the production of correctly assembled VLPs. A structured mathematical model describing the relevant intracellular processes (baculovirus adsorption and trafficking, DNA replication and gene expression) was employed. Some intracellular processes take several hours for completion and may be regarded as pure time delays. A modified 4th/5th order Runge-Kutta solver was employed to integrate the ODEs system with pure time delays. A coinfection program using different combinations of multiplicity of infection (MOI) for each gene (vp2, vp6 and vp7) was investigated. The best results were obtained for MOI combinations of 2 (vp2)+5 (vp6)+8 (vp7) or 5+2+8. It was also concluded that viral protein 7 (VP7) was the limiting component for VLPs assembly. This study highlights the usefulness of mathematical modeling in the design of improved infection strategies for VLPs production.

Original languageEnglish
Pages (from-to)1673-1678
Number of pages6
JournalComputer Aided Chemical Engineering
Volume21
Issue numberC
DOIs
Publication statusPublished - 2006

Fingerprint

Proteins
Time delay
Viral Proteins
Viruses
Gene expression
DNA
Genes
Mathematical models
Adsorption

Keywords

  • assembly
  • modeling
  • Rotavirus
  • simulation
  • VLP

Cite this

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title = "Rotavirus-like particle production: Simulation of protein production and particle assembly",
abstract = "In this work we study the production of rotavirus virus-like particles (VLP) using the baculovirus expression vector system (BEVS). A model-based optimization of the infection strategy was performed in order to maximize the production of correctly assembled VLPs. A structured mathematical model describing the relevant intracellular processes (baculovirus adsorption and trafficking, DNA replication and gene expression) was employed. Some intracellular processes take several hours for completion and may be regarded as pure time delays. A modified 4th/5th order Runge-Kutta solver was employed to integrate the ODEs system with pure time delays. A coinfection program using different combinations of multiplicity of infection (MOI) for each gene (vp2, vp6 and vp7) was investigated. The best results were obtained for MOI combinations of 2 (vp2)+5 (vp6)+8 (vp7) or 5+2+8. It was also concluded that viral protein 7 (VP7) was the limiting component for VLPs assembly. This study highlights the usefulness of mathematical modeling in the design of improved infection strategies for VLPs production.",
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author = "Ant{\'o}nio Rold{\~a}o and Vieira, {Helena L A} and Carrondo, {Manuel J T} and Alves, {Paula M.} and R. Oliveira",
year = "2006",
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AU - Alves, Paula M.

AU - Oliveira, R.

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