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Spatial Metabolomics Reveals Localized Impact of Influenza Virus Infection on the Lung Tissue Metabolome
The influenza virus (IAV) is a major cause of respiratory disease, with significant infection increases in pandemic years. Vaccines are a mainstay of IAV prevention but are complicated by IAV’s vast strain diversity and manufacturing and vaccine uptake limitations. While antivirals may be used for t...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society for Microbiology
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9426520/ https://www.ncbi.nlm.nih.gov/pubmed/35730946 http://dx.doi.org/10.1128/msystems.00353-22 |
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author | Dean, Danya A. Klechka, London Hossain, Ekram Parab, Adwaita R. Eaton, Krystin Hinsdale, Myron McCall, Laura-Isobel |
author_facet | Dean, Danya A. Klechka, London Hossain, Ekram Parab, Adwaita R. Eaton, Krystin Hinsdale, Myron McCall, Laura-Isobel |
author_sort | Dean, Danya A. |
collection | PubMed |
description | The influenza virus (IAV) is a major cause of respiratory disease, with significant infection increases in pandemic years. Vaccines are a mainstay of IAV prevention but are complicated by IAV’s vast strain diversity and manufacturing and vaccine uptake limitations. While antivirals may be used for treatment of IAV, they are most effective in early stages of the infection, and several virus strains have become drug resistant. Therefore, there is a need for advances in IAV treatment, especially host-directed therapeutics. Given the spatial dynamics of IAV infection and the relationship between viral spatial distribution and disease severity, a spatial approach is necessary to expand our understanding of IAV pathogenesis. We used spatial metabolomics to address this issue. Spatial metabolomics combines liquid chromatography-tandem mass spectrometry of metabolites extracted from systematic organ sections, 3D models, and computational techniques to develop spatial models of metabolite location and their role in organ function and disease pathogenesis. In this project, we analyzed serum and systematically sectioned lung tissue samples from uninfected or infected mice. Spatial mapping of sites of metabolic perturbations revealed significantly lower metabolic perturbation in the trachea compared to other lung tissue sites. Using random forest machine learning, we identified metabolites that responded differently in each lung position based on infection, including specific amino acids, lipids and lipid-like molecules, and nucleosides. These results support the implementation of spatial metabolomics to understand metabolic changes upon respiratory virus infection. IMPORTANCE The influenza virus is a major health concern. Over 1 billion people become infected annually despite the wide distribution of vaccines, and antiviral agents are insufficient to address current clinical needs. In this study, we used spatial metabolomics to understand changes in the lung and serum metabolome of mice infected with influenza A virus compared to uninfected controls. We determined metabolites altered by infection in specific lung tissue sites and distinguished metabolites perturbed by infection between lung tissue and serum samples. Our findings highlight the utility of a spatial approach to understanding the intersection between the lung metabolome, viral infection, and disease severity. Ultimately, this approach will expand our understanding of respiratory disease pathogenesis. |
format | Online Article Text |
id | pubmed-9426520 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | American Society for Microbiology |
record_format | MEDLINE/PubMed |
spelling | pubmed-94265202022-08-31 Spatial Metabolomics Reveals Localized Impact of Influenza Virus Infection on the Lung Tissue Metabolome Dean, Danya A. Klechka, London Hossain, Ekram Parab, Adwaita R. Eaton, Krystin Hinsdale, Myron McCall, Laura-Isobel mSystems Research Article The influenza virus (IAV) is a major cause of respiratory disease, with significant infection increases in pandemic years. Vaccines are a mainstay of IAV prevention but are complicated by IAV’s vast strain diversity and manufacturing and vaccine uptake limitations. While antivirals may be used for treatment of IAV, they are most effective in early stages of the infection, and several virus strains have become drug resistant. Therefore, there is a need for advances in IAV treatment, especially host-directed therapeutics. Given the spatial dynamics of IAV infection and the relationship between viral spatial distribution and disease severity, a spatial approach is necessary to expand our understanding of IAV pathogenesis. We used spatial metabolomics to address this issue. Spatial metabolomics combines liquid chromatography-tandem mass spectrometry of metabolites extracted from systematic organ sections, 3D models, and computational techniques to develop spatial models of metabolite location and their role in organ function and disease pathogenesis. In this project, we analyzed serum and systematically sectioned lung tissue samples from uninfected or infected mice. Spatial mapping of sites of metabolic perturbations revealed significantly lower metabolic perturbation in the trachea compared to other lung tissue sites. Using random forest machine learning, we identified metabolites that responded differently in each lung position based on infection, including specific amino acids, lipids and lipid-like molecules, and nucleosides. These results support the implementation of spatial metabolomics to understand metabolic changes upon respiratory virus infection. IMPORTANCE The influenza virus is a major health concern. Over 1 billion people become infected annually despite the wide distribution of vaccines, and antiviral agents are insufficient to address current clinical needs. In this study, we used spatial metabolomics to understand changes in the lung and serum metabolome of mice infected with influenza A virus compared to uninfected controls. We determined metabolites altered by infection in specific lung tissue sites and distinguished metabolites perturbed by infection between lung tissue and serum samples. Our findings highlight the utility of a spatial approach to understanding the intersection between the lung metabolome, viral infection, and disease severity. Ultimately, this approach will expand our understanding of respiratory disease pathogenesis. American Society for Microbiology 2022-06-22 /pmc/articles/PMC9426520/ /pubmed/35730946 http://dx.doi.org/10.1128/msystems.00353-22 Text en Copyright © 2022 Dean et al. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Research Article Dean, Danya A. Klechka, London Hossain, Ekram Parab, Adwaita R. Eaton, Krystin Hinsdale, Myron McCall, Laura-Isobel Spatial Metabolomics Reveals Localized Impact of Influenza Virus Infection on the Lung Tissue Metabolome |
title | Spatial Metabolomics Reveals Localized Impact of Influenza Virus Infection on the Lung Tissue Metabolome |
title_full | Spatial Metabolomics Reveals Localized Impact of Influenza Virus Infection on the Lung Tissue Metabolome |
title_fullStr | Spatial Metabolomics Reveals Localized Impact of Influenza Virus Infection on the Lung Tissue Metabolome |
title_full_unstemmed | Spatial Metabolomics Reveals Localized Impact of Influenza Virus Infection on the Lung Tissue Metabolome |
title_short | Spatial Metabolomics Reveals Localized Impact of Influenza Virus Infection on the Lung Tissue Metabolome |
title_sort | spatial metabolomics reveals localized impact of influenza virus infection on the lung tissue metabolome |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9426520/ https://www.ncbi.nlm.nih.gov/pubmed/35730946 http://dx.doi.org/10.1128/msystems.00353-22 |
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