الوصف: |
Increasingly, mathematical models of viral infections have come to recognise the important role of spatial structure in infection dynamics. Almost invariably, spatial models of viral infections make use of a wide, flat computational domain which is assumed to be representative of the entire affected tissue. Implicit in this assumption is that either the tissue being modelled is largely wide and homogeneous, or that the topology of the tissue has little influence on the dynamics of the system. This assumption fails to take into account the distinctive geometry of the lung. The lung is characterised by a tubular, highly branching structure, and moreover is spatially heterogeneous: deeper regions of the lung are composed of far narrower airways and are associated with more severe infection. Here, we extend a typical multicellular model of viral dynamics to account for two essential features of the geometry of the lung: the tubular structure of airways, and the branching process between airway generations. We show that, with this more realistic tissue geometry, the dynamics of infection are substantially changed compared to the standard approach, and that the resulting model is equipped to tackle important biological phenomena that are not well-addressed with existing models, including viral lineage dynamics in the lung, and heterogeneity in immune responses to infection in different regions of the respiratory tree. |