Exploring the effect of biological delays in kinetic models of influenza within a host or cell culture

Holder, Benjamin P.; Beauchemin, Catherine A. A.
January 2011
BMC Public Health;2011 Supplement 1, Vol. 11 Issue Suppl 1, p1
Academic Journal
Background: For a typical influenza infection in vivo, viral titers over time are characterized by 1-2 days of exponential growth followed by an exponential decay. This simple dynamic can be reproduced by a broad range of mathematical models which makes model selection and the extraction of biologically-relevant infection parameters from experimental data difficult. Results: We analyze in vitro experimental data from the literature, specifically that of single-cycle viral yield experiments, to narrow the range of realistic models of infection. In particular, we demonstrate the viability of using a normal or lognormal distribution for the time a cell spends in a given infection state (e.g., the time spent by a newly infected cell in the latent state before it begins to produce virus), while exposing the shortcomings of ordinary differential equation models which implicitly utilize exponential distributions and delay-differential equation models with fixed-length delays. Conclusions: By fitting published viral titer data from challenge experiments in human volunteers, we show that alternative models can lead to different estimates of the key infection parameters.


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