Premium
A mathematical model of the trafficking of acid‐dependent enveloped viruses: Application to the binding, uptake, and nuclear accumulation of baculovirus
Author(s) -
Dee Kennie U.,
Shuler Michael L.
Publication year - 1997
Publication title -
biotechnology and bioengineering
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.136
H-Index - 189
eISSN - 1097-0290
pISSN - 0006-3592
DOI - 10.1002/(sici)1097-0290(19970605)54:5<468::aid-bit7>3.0.co;2-c
Subject(s) - endocytosis , semliki forest virus , viral envelope , biology , virus , internalization , endosome , microbiology and biotechnology , lipid bilayer fusion , viral entry , virology , nuclear transport , receptor , viral replication , rna , cell nucleus , gene , biochemistry , cytoplasm
A quantitative understanding of virus trafficking would be useful in treating viral‐mediated diseases, developing protocols for viral gene therapy, designing infection regimens for viral expression systems, and optimizing vaccine and recombinant protein production. Here, we present a mathematical model of the attachment, internalization, endosomal fusion, lysosomal routing, and nuclear accumulation of baculovirus in SF21 insect cells. The model accounts for multivalent bond formation of the virus with cell surface receptors. The model mimics accurately the experimental trafficking dynamics of the virus at both low and high virion to cell ratios, and estimates a receptor number of 11,000 per cell. A significant amount of virus was degraded intracellularly. Independent of the virion to cell ratio, half of the internalized virus was degraded with the rest accumulating in the nucleus. The formalism used in the model may be generally useful for other acid‐dependent enveloped viruses. A subset of the model has been used previously to describe the trafficking of Semliki Forest virus, an acid‐dependent enveloped RNA virus. Two pathways have previously been implicated for the in vitro entry of the budded form of the baculovirus: adsorptive endocytosis and plasma membrane fusion. Experimental evidence is presented which strongly suggests that the physical number of viruses entering by plasma membrane fusion is not significant relative to receptor‐mediated endocytosis. © 1997 John Wiley & Sons, Inc., Biotechnol Bioeng 54: 468–490, 1997.