A kinetic and statistical-thermodynamic model for baculovirus infection and virus-like particle assembly in suspended insect cells

Virus-like particles (VLPs) are self-assembled structures comprised of virus capsid proteins that closely resemble native virus but are devoid of native viral RNA or DNA and therefore have attracted significant attention as noninfectious vaccines. A mathematical model that characterizes baculovirus infection, protein synthesis and VLP assembly in insect cells was developed. The probability of infection was described by a Poisson distribution and the infected cell population was segregated by the time of infection and the number of infecting viruses in order to examine the contributions of individual cells. Predictions relating to cell growth, virus infection efficiency (tracked by immunofluorescence labeling), replication kinetics, substrate consumption, and cell death in suspended batch cultures agreed well with experiments. For efficient primary infection with virus, a multiplicity of infection (MOI) of 2.5 was necessary. The optimal harvest timing occurred at 40-70% cell viability. The assembly of VLPs comprised of the structural proteins (VP2 and VP3) of the infectious bursal disease virus (IBDV) using a thermodynamically based equilibrium model was described. The complete model suggested that the formation of IBD VLP was thermodynamically favorable and predicted well the baculovirus infection in individual cells or in the culture as a whole. This model can potentially be used to further describe and optimize VLP formation for other virus pathogens. (C) 2000 Elsevier Science Ltd. All rights reserved.