A structured review of baculovirus infection process: integration of mathematical models and biomolecular information on cell-virus interaction.

The baculovirus expression vector system (BEVS) is an emerging tool for the production of recombinant proteins, vaccines and bio-pesticides. However, a system-level understanding of the complex infection process is important in realizing large-scale production at a lower cost. The entire baculovirus infection process is summarized as a combination of various modules and the existing mathematical models are discussed in light of these modules. This covers a systematic review of the present understanding of virus internalization, viral DNA replication, protein expression, budded virus (BV) and occlusion-derived virus (ODV) formation, few polyhedral (FP) and defective interfering particle (DIP) mutant formation, cell cycle modification and apoptosis during the viral infection process. The corresponding theoretical models are also included. Current knowledge regarding the molecular biology of the baculovirus/insect cell system is integrated with population balance and mass action kinetics models. Furthermore, the key steps for simulating cell and virus densities and their underlying features are discussed. This review may facilitate the further development and refinement of mathematical models, thereby providing the basis for enhanced control and optimization of bioreactor operation.