MATHEMATICAL-MODEL OF THE TRAFFICKING OF ACID-DEPENDENT ENVELOPED VIRUSES - APPLICATION TO THE BINDING, UPTAKE, AND NUCLEAR ACCUMULATION OFBACULOVIRUS

A quantitative understanding of virus trafficking would be useful in t reating viral-mediated diseases, developing protocols for viral gene t herapy, designing infection regimens for viral expression systems, and optimizing vaccine and recombinant protein production. Here, we prese nt 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 o f the virus with cell surface receptors. The model mimics accurately t he 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. Inde pendent of the virion to cell ratio, half of the internalized virus wa s degraded with the rest accumulating in the nucleus. The formalism us ed in the model may be generally useful for other acid-dependent envel oped viruses. A subset of the model has been used previously to descri be the trafficking of Semliki Forest virus, an acid-dependent envelope d RNA virus. Two pathways have previously been implicated for the in v itro entry of the budded form of the baculovirus: adsorptive endocytos is and plasma membrane fusion. Experimental evidence is presented whic h strongly suggests that the physical number of viruses entering by pl asma membrane fusion is not significant relative to receptor-mediated endocytosis, (C) 1997 John Wiley & Sons, Inc.