摘要
The death of cultured insect cells after baculovirus infection is a time‐dependent event. Without a quantitative model, it is difficult to characterize its kinetics. Our group has shown that the cell survival rate can be characterized by use of the n‐target theory, which involves only two parameters: the number of hypothetical inactivation targets (n) and the first‐order death rate (k). In this study, we used different recombinant viruses to examine the effect of heterologous protein expression on the cell survival rate. The proteins expressed were β‐galactosidase, human T‐cell leukemia virus type I p40 x , human interleukin‐2, and human tissue plasminogen activator (tPA). The survival rate was affected by protein expression, but the n value remained constant if the protein expression level was high (above 30 mg/L). Low‐level expression of secreted, glycosylated tPA resulted in a reduced n value, which was restored to the normal value when the tPA signal peptide and prosequence were deleted. In addition, if the n value was normal (10–11), the level of protein expression correlated negatively with the death rate. However, if the n value was reduced by unfavorable culture conditions or foreign protein expression, the expression level correlated positively with the death rate. A dimensionless plot with kt as the dimensionless time shows that alteration of the k value while retaining constant n is equivalent to a rescaling of time. Therefore, the survival curves with constant n reduce to a single curve on the dimensionless plot. Although the underlying mechanisms affecting n and k are still unknown, this study shows that they can serve as convenient phenotypes for investigating virus—host interactions. Copyright © 1994 American Institute of Chemical Engineers (AIChE)