Rate-equation modelling and ensemble approach to extraction of parameters for viral infection-induced cell apoptosis and necrosis

Abstract

We develop a theoretical approach that uses physiochemical kinetics modelling to describe cell population dynamics upon progression of viral infection in cell culture, which results in cell apoptosis (programmed cell death) and necrosis (direct cell death). Several model parameters necessary for computer simulation were determined by reviewing and analyzing available published experimental data. By comparing experimental data to computer modelling results, we identify the parameters that are the most sensitive to the measured system properties and allow for the best data fitting. Our model allows extraction of parameters from experimental data and also has predictive power. Using the model we describe interesting time-dependent quantities that were not directly measured in the experiment and identify correlations among the fitted parameter values. Numerical simulation of viral infection progression is done by a rate-equation approach resulting in a system of "stiff" equations, which are solved by using a novel variant of the stochastic ensemble modelling approach. The latter was originally developed for coupled chemical reactions.

SIRT6 knockout cells resist apoptosis initiation but not progression: a computational method to evaluate the progression of apoptosis

“…It is noteworthy that the values of Q, G, L are comparable to estimates obtained in our previous study [17] that used a similar numerical model to describe chicken fibroblast death due to Bursal disease virus infection. Specifically, the value for the rate of apoptosis progression, 𝐺𝐺 = 0.0303 hour −1 , fitted for the present data for WT serum-starved cells is close to that in [17], 𝐺𝐺 = 0.0231 hour −1 , suggesting some sort of "universality" of the rates of cell-death processes. The rate of apoptosis initiation (rate Q, Fig.…”

“…The rate of cell division (fitted parameter R) is much smaller than a typical value for cells not subject to stresses [17]. This is consistent with the observation that growth signaling provided by fetal bovine serum is necessary for rapid cell division [18].…”

“…The rate of apoptosis initiation (rate Q, Fig. 3B) is also close to that of "highlyinfected" cells [17].…”