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Stochastic Modelling of the Intracellular Replication of Influenza Virsu during Vaccine Production


Dorl,  Sebastian
Bioprocess Engineering, Max Planck Institute for Dynamics of Complex Technical Systems, Max Planck Society;

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Dorl, S. (2013). Stochastic Modelling of the Intracellular Replication of Influenza Virsu during Vaccine Production. Bachelor Thesis, Otto-von-Guericke-Universität, Magdeburg.

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We performed stochastic simulations of a mathematical model of influenza A infection in mammalian cells that incorporates virus entry, viral replication, and virion release on a single-cell level. Simulations were conducted using tau-leaping (a variation of the Gillespie algorithm) and initial conditions corresponding to an MOI of 1, 3, and 10 respectively. Results for high MOI were equivalent to comparable deterministic simula- tions. However, predicted virus yields dropped significantly in low MOI situations due to virion degradation in endosomes and an increase of variance in virus entry time. Our findings highlight the role of the MOI as a process parameter with complex effects on virus entry dynamics. In contrast, the dynamics of viral replication were observed to vary little between individual simulations with the onset time of replication showing the greatest difference. Analysis of the time course of variance revealed that the distribution width of viral components increases during early replication but starts to monotonically decrease at later time points. We propose that the regulatory effect of the matrix protein M1 is a major factor in reducing noise created by stochastic effects in influenza virus in- fection. These findings take a step towards quantifying the intrinsic sources of stochastic fluctuations during the intracellular influenza virus life cycle.