HYPOTHESIS AND THEORY article
Front. Virol.
Sec. Bioinformatic and Predictive Virology
This article is part of the Research TopicBioinformatics Tools to Describe Microbial InteractionsView all articles
Multicompartment Modeling of Influenza A Replication Along the Murine Respiratory Tract
Provisionally accepted
- Systems Medicine of Infectious Diseases, University of Idaho, Moscow, United States
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Influenza A virus spreads through the respiratory tract in a compartment-specific manner, yet the mechanisms governing its progression remain unclear. Here, we investigated how viral replication and inter-compartment transport shape infection dynamics across the nose, trachea, and lungs. To address this, we developed a multicompartment mathematical model based on a target-cell framework and fitted it to reported viral-load data from mice infected with the Udorn H3N2 strain, using bootstrap estimation to quantify uncertainty. The best-performing model revealed rapid amplification and substantial target-cell depletion in the nose, limited replication, and delayed viral dynamics in the lungs, mainly driven by input from upstream compartments. Transport parameters exceeded local replication rates in deeper regions, indicating that the nose serves as the primary site of viral replication and seeding. Overall, this study highlights the dominant role of the nasal compartment in driving within-host influenza progression.
Keywords: H3N2, influenza, lungs, mathematical modeling, Nose, ODE, Respiratory Tract Microbiota, Trachea
Received: 22 Dec 2025; Accepted: 11 Feb 2026.
Copyright: © 2026 Blanco-Rodriguez, Chi Uluac and Hernandez-Vargas. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Esteban A. Hernandez-Vargas
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