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A mathematical model describing the localization and spread of influenza A virus infection within the human respiratory tract

Within the human respiratory tract (HRT), viruses diffuse through the periciliary fluid (PCF) bathing the epithelium, and travel upwards via advection towards the nose and mouth, as the mucus escalator entrains the PCF. While many mathematical models (MMs) to date have described the course of influenza A virus (IAV) infections in vivo, none have considered the impact of both diffusion and advection on the kinetics and localization of the infection. The MM herein represents the HRT as a one-dimensional track extending from the nose down to a depth of 30 cm, wherein stationary cells interact with the concentration of IAV which move along within the PCF. When IAV advection and diffusion are both considered, the former is found to dominate infection kinetics, and a 10-fold increase in the virus production rate is required to counter its effects. The MM predicts that advection prevents infection from disseminating below the depth at which virus first deposits. Because virus is entrained upwards, the upper HRT sees the most virus, whereas the lower HRT sees far less. As such, infection peaks and resolves faster in the upper than in the lower HRT, making it appear as though infection progresses from the upper towards the lower HRT. When the spatial MM is expanded to include cellular regeneration and an immune response, it can capture the time course of infection with a seasonal and an avian IAV strain by shifting parameters in a manner consistent with what is expected to differ between these two types of infection. The impact of antiviral therapy with neuraminidase inhibitors was also investigated. This new MM offers a convenient and unique platform from which to study the localization and spread of respiratory viral infections within the HRT.

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