Model for Virus Infection

As in the previous model for the virus production we established a ODE model based on the law of mass action. The following paragraph explains the reaction scheme and our model assumptions. In the subsequent paragraphs the system of differential equations is specified and the implementation in MathWorks® MATLAB is discussed.
The last section deals with our modeling results.

Reaction Scheme

Reduced Reaction Scheme

Reducing the complexity of virus production we divide the cell into three compartments: the extracellular matrix (all quantities with the index ext), the cytoplasm (cyt) and the nucleus (nuc). Four plasmids are transfected - the plasmid coding for the helper proteins (helper), the gene of interest (goi) and two types of plasmids coding for the capsid proteins (capwt [wild type], capmod [modified]).
The plasmids are transported into the nucleus where gene expression is initiated. Processed mRNA is transported into the cytoplasm and proteins (phelper, pcapwt, pcapmod) are produced. Containing a nuclear localization sequence proteins are relocated into the nucleus where capsid assembly occurs. The viral capsid is compose of 60 subunits of viral coat proteins. Titration of the two plasmids coding for the capsid proteins leads to virus surfaces with different ratios of wild type and modified capsid proteins.
The gene of interest is replicated by cellular polymerases and single stranded DNA (ssDNA) is encapsidated into the preformed capsids (capsid) forming infectious viral particles (V).
Finally the recombinant viruses are released into the extracellular matrix and can be harvested for transduction.

Differential Equations

Methods and Simulation

The ODE model was implemented in MathWorks® MATLAB R2010b. Integration of the differential equations was achieved using the stiff integrator ode15s with automatic integration step size management.
To calibrate the dynamics of the mathematical model to those of biological system we used time lapse data of fluorescence experiments as well as published values for the rate constants.

The parameters used are given in the table below. Also you can download the MATLAB source code.

get the .m-File (MATLAB source code)

Results and Discussion