Virus dynamics: Basic and detailed models of influenza A virus replication in mammalian cells

Poster number: 6

Udo Reichl

  1. Max-Planck-Institute for Dynamics of Complex Technical Systems, Magdeburg, Germany

Mathematical modeling is of crucial importance for a quantitative understanding of the enormous complexity of virus host-cell interaction. In addition, design and control of viral-based cell culture processes for vaccine production and gene therapy as well as further improvement of antiviral therapies can be supported by such models.

Here we report on modeling aspects of the replication of influenza A virus in mammalian cells. Main focus is on basic and highly structured models describing virus replication in bioreactors as well as virus life cycle in a single cell. The first model considers the following state variables: un­in­fected cells, infected cells, infectious virus particles and total virions. The model describes the time course of un­in­fected and infected cells as well as virus propagation in a bioreactor. Simulation studies suggest that small variations (<10%) in initial conditions and parameters do not influence viral yields significantly. Main parameters relevant for process optimization are the specific rate of virus replication and the specific cell death rate due to infection. The second model accounts for individual steps such as virus attachment, internalization, genome replication and translation as well as progeny virion assembly. The model describes an average cell surrounded by a small quantity of medium, which is infected by a low number of virus particles. Simulation results show that surface receptors and endosomes, as well as the cellular pools of free nucleotides and amino acids, are not significantly influenced during the first hours of virus replication. A factor that limits the growth rate of progeny viruses and their release is the total amount of matrix proteins (M1) in the nucleus while other newly synthesized viral proteins (e.g. nucleoprotein NP) and viral RNAs accumulate. During budding synthesis of vRNPs represents another bottleneck.