Stochastic simulation of protein expression in the baculovirus/insect cells system

In this paper, a stochastic dynamical model for heterologous protein expression in the baculovirus/insect cells system is presented. The model describes foreign protein expression under the control of the polyhedrin promoter, which is the most commonly used promoter in this system. The present study explores the hypothesis of gene size being the main factor affecting the rate of protein expression in the host cell. The infection process, prior to protein expression, is of stochastic nature. Thus, the combination of infection and intracellular dynamics results in a complex stochastic/structured dynamical model which is very challenging in a systems engineering perspective. Due to the randomness of virus binding to the host cells, the intracellular dynamics of individual cells show unique patterns, potentially leading to a very large scale stochastic problem. The size of the problem was reduced by considering a finite number of subpopulations of “equal” cells. A discrete time formulation was adopted for realization of the stochastic infection and numerical integration. The method is illustrated by the application to the production of viral protein 2 (vp2) in suspended cultures of Spodoptera frugiperda Sf-9 cells infected with recombinant Autographa californica multiple nucleopolyhedrovirus (AcMNPV) coding for vp2.