Accounting for the geometry of the respiratory tract in viral infections

Abstract

Increasingly, experimentalists and modellers alike have come to recognise the important role of spatial structure in infection dynamics. Almost invariably, spatial computational models of viral infections — as with in vitro experimental systems — represent the tissue as wide and flat, which is often assumed to be representative of the entire affected tissue within the host. However, this assumption fails to take into account the distinctive geometry of the respiratory tract in the context of viral infections. The respiratory tract is characterised by a tubular, 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 respiratory tract: 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 standard computational and experimental approaches, and that the resulting model is equipped to tackle important biological phenomena that do not arise in a flat host tissue, including viral lineage dynamics, and heterogeneity in immune responses to infection in different regions of the respiratory tree. Our findings suggest aspects of viral dynamics which current in vitro systems may be insufficient to describe, and points to several features of respiratory infections which can be experimentally assessed.