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Multiomics analysis unveils key biomarkers during dynamic progress of IAV infection in mice

ABSTRACT: Murine IAV infection models are vital for influenza research, but biomarker progression during the disease is unclear. This study aims to help improve disease surveillance and treatment outcome assessment by understanding viral infection dynamics and biological shifts from mild to severe symptoms in mouse models. The physiological parameters, viral load, inflammatory responses, and histopathological changes were evaluated in Balb/c mice infected with IAV over 14 days period. Intervention within 6 days after influenza virus infection is crucial to prevent severe illness. Using DIABLO multi-omics analysis, we analyzed transcriptomic and metabolomic data from mouse lung tissues and serum metabolomic data at 4, 6, 8, and 10 days post-infection. Several key biomarkers like Ccl8, Pdcd1, Gzmk, Kynurenine, L-Glutamine were identified during influenza infection. The serum-based influenza progression scoring system developed in this study provides precise treatment strategies and personalized plans for clinical management. This scoring system detects when the levels of L-Glutamine, adipoyl-carnitine, triacetic acid lactone, and isopropanol in the serum exceed 2.5 times the normal range, indicating that the patient is in the influenza infection phase (days 4-6). Intervening during this phase can effectively prevent the condition from deteriorating into a critical stage.

ORGANISM(S): Mus musculus

PROVIDER: GSE292329 | GEO | 2025/05/08

REPOSITORIES: GEO

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Project description:Miao2010 - Innate and adaptive immune responses to primary Influenza A Virus infection This model is described in the article: Quantifying the early immune response and adaptive immune response kinetics in mice infected with influenza A virus. Miao H, Hollenbaugh JA, Zand MS, Holden-Wiltse J, Mosmann TR, Perelson AS, Wu H, Topham DJ. J. Virol. 2010 Jul; 84(13): 6687-6698 Abstract: Seasonal and pandemic influenza A virus (IAV) continues to be a public health threat. However, we lack a detailed and quantitative understanding of the immune response kinetics to IAV infection and which biological parameters most strongly influence infection outcomes. To address these issues, we use modeling approaches combined with experimental data to quantitatively investigate the innate and adaptive immune responses to primary IAV infection. Mathematical models were developed to describe the dynamic interactions between target (epithelial) cells, influenza virus, cytotoxic T lymphocytes (CTLs), and virus-specific IgG and IgM. IAV and immune kinetic parameters were estimated by fitting models to a large data set obtained from primary H3N2 IAV infection of 340 mice. Prior to a detectable virus-specific immune response (before day 5), the estimated half-life of infected epithelial cells is approximately 1.2 days, and the half-life of free infectious IAV is approximately 4 h. During the adaptive immune response (after day 5), the average half-life of infected epithelial cells is approximately 0.5 days, and the average half-life of free infectious virus is approximately 1.8 min. During the adaptive phase, model fitting confirms that CD8(+) CTLs are crucial for limiting infected cells, while virus-specific IgM regulates free IAV levels. This may imply that CD4 T cells and class-switched IgG antibodies are more relevant for generating IAV-specific memory and preventing future infection via a more rapid secondary immune response. Also, simulation studies were performed to understand the relative contributions of biological parameters to IAV clearance. This study provides a basis to better understand and predict influenza virus immunity. This model is hosted on BioModels Database and identified by: BIOMD0000000546. To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

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Multiomics analysis unveils key biomarkers during dynamic progress of IAV infection in mice

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