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Article

Modelling the Effect of MUC1 on Influenza Virus Infection Kinetics and Macrophage Dynamics

by 1,*, 1 and 1,2,3
1
School of Mathematics and Statistics, The University of Melbourne, Parkville, VIC 3010, Australia
2
Peter Doherty Institute for Infection and Immunity, The Royal Melbourne Hospital and The University of Melbourne, Parkville, VIC 3010, Australia
3
Melbourne School of Population and Global Health, The University of Melbourne, Parkville, VIC 3010, Australia
*
Author to whom correspondence should be addressed.
Academic Editors: Amber M. Smith and Ruian Ke
Viruses 2021, 13(5), 850; https://doi.org/10.3390/v13050850
Received: 25 March 2021 / Revised: 20 April 2021 / Accepted: 4 May 2021 / Published: 7 May 2021
(This article belongs to the Special Issue Mathematical Modeling of Viral Infection)
MUC1 belongs to the family of cell surface (cs-) mucins. Experimental evidence indicates that its presence reduces in vivo influenza viral infection severity. However, the mechanisms by which MUC1 influences viral dynamics and the host immune response are not yet well understood, limiting our ability to predict the efficacy of potential treatments that target MUC1. To address this limitation, we use available in vivo kinetic data for both virus and macrophage populations in wildtype and MUC1 knockout mice. We apply two mathematical models of within-host influenza dynamics to this data. The models differ in how they categorise the mechanisms of viral control. Both models provide evidence that MUC1 reduces the susceptibility of epithelial cells to influenza virus and regulates macrophage recruitment. Furthermore, we predict and compare some key infection-related quantities between the two mice groups. We find that MUC1 significantly reduces the basic reproduction number of viral replication as well as the number of cumulative macrophages but has little impact on the cumulative viral load. Our analyses suggest that the viral replication rate in the early stages of infection influences the kinetics of the host immune response, with consequences for infection outcomes, such as severity. We also show that MUC1 plays a strong anti-inflammatory role in the regulation of the host immune response. This study improves our understanding of the dynamic role of MUC1 against influenza infection and may support the development of novel antiviral treatments and immunomodulators that target MUC1. View Full-Text
Keywords: influenza viral dynamics; cell-surface mucin MUC1; immune response; mathematical models influenza viral dynamics; cell-surface mucin MUC1; immune response; mathematical models
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MDPI and ACS Style

Li, K.; Cao, P.; McCaw, J.M. Modelling the Effect of MUC1 on Influenza Virus Infection Kinetics and Macrophage Dynamics. Viruses 2021, 13, 850. https://doi.org/10.3390/v13050850

AMA Style

Li K, Cao P, McCaw JM. Modelling the Effect of MUC1 on Influenza Virus Infection Kinetics and Macrophage Dynamics. Viruses. 2021; 13(5):850. https://doi.org/10.3390/v13050850

Chicago/Turabian Style

Li, Ke, Pengxing Cao, and James M. McCaw 2021. "Modelling the Effect of MUC1 on Influenza Virus Infection Kinetics and Macrophage Dynamics" Viruses 13, no. 5: 850. https://doi.org/10.3390/v13050850

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