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ISSN
1672-9145
Acta Biochim Biophys Sin
2004, 36(11): 729–740
CN 31-1940/Q
A Mathematical Model of Baculovirus Infection on Insect Cells at Low
Multiplicity of Infection
You-Hong ZHANG1,2*
and José C. MERCHUK3
1Hubei Key
Laboratory of Novel Chemical Reactor & Green Chemical Technology, Wuhan
Institute of Technology, Wuhan 430073, China;
2Department
of Biotechnology Engineering, 3Department of Chemical Engineering,
Ben-Gurion University of the Negev, P.O. Box 653, Beer-Sheva 84105, Israel
Abstract The expression efficiency of the insect cells-baculovirus system
used for insecticidal virus production and the expression of medically useful foreign
genes is closely related with the dynamics of infection. The present studies
develop a model of the dynamic process of insect cell infection with
baculovirus at low multiplicity of infection (MOI), which is based on the
multi-infection cycles of insect cell infection at low MOI. A mathematical
model for the amount of viruses released from primary infected cells and the
amount of free viruses before secondary infected cells release viruses has been
developed. Comparison of the simulation results with the experimental data
confirms qualitatively that this model is highly reasonable before secondary
infected cells release viruses. This model is considered as a base for further
modeling the entire complicated infection process.
Key words modeling; infection;
insect cells; baculovirus; multiplicity of infection (MOI)
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Received: July 15, 2004 Accepted: October 14,
2004
Nomenclatures: C, cell concentration (cells/ml); Ci, cell initial concentration (cells/ml); Cin(t), total number of primarily infected cells (PIC) per ml
till t (cells/ml); FIC, first infection cycle; hpi, hours post
infection; MOI, multiplicity of infection (TCID50/cells);
NOVs, non-occluded viruses (TCID50/ml); OVs, occluded viruses
(OVs/ml); PICs, primary infected cells; PIP, primary infection process; QP,
total amount of viruses released from PICs till time t (TCID50/ml); SIC, second infection cycle; SICs, secondary infected cells;
SIP, secondary infection process; TCID50, tissue culture
infective dose 50% units; TOI, time of infection (h); t, time variable
(h); t1, infection time of a cell (h); V,
volume of culture system (ml); v, unbound virus concentration, i.e. free
virus concentration (TCID50/ml); vi, concentration of viruses initially added (TCID50/ml); x, time for virus release of an infected cell (h); aA, first
order virus binding coefficient (h–1); aP,
maximum virus release rate coefficient (TCID50・cells–1・h–1); specific cell growth rate (h–1); tVE, time period from the attachment of a virus to a cell to the end of
virus budding by the infected cell (h); tVP, time period from the
beginning to the end of virus budding (h); tVR, time period from the
attachment of a virus to the budding of new virus (h); y(x), virus release
rate by an infected cell (TCID50・cells–1・h–1)
*Corresponding author: Tel, 86-27-62330622; Fax, 86-27-87194465;
E-mail, [email protected]