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ISSN 1672-9145 Acta Biochim Biophys Sin 2004, 36(11): 729-740 CN 31-1940/Q

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A Mathematical Model of Baculovirus Infection on Insect Cells at Low Multiplicity of Infection

You-Hong ZHANG^1,2* 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]