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Nonclassical autophagy activation pathways are essential for production of infectious Influenza A virus in vitro

Autophagy is a critical mechanism deployed by eukaryotic cells in response to stress, including viral infection, to boost the innate antimicrobial responses. However, an increasing number of pathogens hijack the autophagic machinery to facilitate their own replication. Influenza A virus (IAV), respo...

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Autores principales: Bell, Tisza A. S., Velappan, Nileena, Gleasner, Cheryl D., Xie, Gang, Starkenburg, Shawn R., Waldo, Geoffrey, Banerjee, Shounak, Micheva‐Viteva, Sofiya N.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9305535/
https://www.ncbi.nlm.nih.gov/pubmed/34931347
http://dx.doi.org/10.1111/mmi.14865
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author Bell, Tisza A. S.
Velappan, Nileena
Gleasner, Cheryl D.
Xie, Gang
Starkenburg, Shawn R.
Waldo, Geoffrey
Banerjee, Shounak
Micheva‐Viteva, Sofiya N.
author_facet Bell, Tisza A. S.
Velappan, Nileena
Gleasner, Cheryl D.
Xie, Gang
Starkenburg, Shawn R.
Waldo, Geoffrey
Banerjee, Shounak
Micheva‐Viteva, Sofiya N.
author_sort Bell, Tisza A. S.
collection PubMed
description Autophagy is a critical mechanism deployed by eukaryotic cells in response to stress, including viral infection, to boost the innate antimicrobial responses. However, an increasing number of pathogens hijack the autophagic machinery to facilitate their own replication. Influenza A virus (IAV), responsible for several global pandemics, has an intricate dependence on autophagy for successful replication in mammalian cells. To elucidate key chokepoints in the host stress responses facilitating IAV replication, we constructed a meta‐transcriptome of IAV and host gene expression dynamics during early (1–3 hpi), mid (4–6 hpi), and late (8–12 hpi) stages of the viral replication cycle at two multiplicities of infection (MOI): 1 and 5. We supplemented the global transcriptome study with phosphoproteomic analysis of stress‐activated protein kinase (SAPK/JNK) signaling in lung carcinoma (predominantly used as an in vitro model of IAV replication) and normal human bronchial epithelial cells. We report significant differences in the activation profiles of autophagy regulating genes upon IAV infection at the two MOI as well as divergent dependence on ULK1 signaling within the normal and cancer cells. Regardless of the cell model, JNK‐Thr187 signaling was crucial for the production of infectious viral particles.
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spelling pubmed-93055352022-07-28 Nonclassical autophagy activation pathways are essential for production of infectious Influenza A virus in vitro Bell, Tisza A. S. Velappan, Nileena Gleasner, Cheryl D. Xie, Gang Starkenburg, Shawn R. Waldo, Geoffrey Banerjee, Shounak Micheva‐Viteva, Sofiya N. Mol Microbiol Research Articles Autophagy is a critical mechanism deployed by eukaryotic cells in response to stress, including viral infection, to boost the innate antimicrobial responses. However, an increasing number of pathogens hijack the autophagic machinery to facilitate their own replication. Influenza A virus (IAV), responsible for several global pandemics, has an intricate dependence on autophagy for successful replication in mammalian cells. To elucidate key chokepoints in the host stress responses facilitating IAV replication, we constructed a meta‐transcriptome of IAV and host gene expression dynamics during early (1–3 hpi), mid (4–6 hpi), and late (8–12 hpi) stages of the viral replication cycle at two multiplicities of infection (MOI): 1 and 5. We supplemented the global transcriptome study with phosphoproteomic analysis of stress‐activated protein kinase (SAPK/JNK) signaling in lung carcinoma (predominantly used as an in vitro model of IAV replication) and normal human bronchial epithelial cells. We report significant differences in the activation profiles of autophagy regulating genes upon IAV infection at the two MOI as well as divergent dependence on ULK1 signaling within the normal and cancer cells. Regardless of the cell model, JNK‐Thr187 signaling was crucial for the production of infectious viral particles. John Wiley and Sons Inc. 2022-01-06 2022-02 /pmc/articles/PMC9305535/ /pubmed/34931347 http://dx.doi.org/10.1111/mmi.14865 Text en © 2021 TRIAD for Los Alamos National Laboratory. Molecular Microbiology published by John Wiley & Sons Ltd. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Research Articles
Bell, Tisza A. S.
Velappan, Nileena
Gleasner, Cheryl D.
Xie, Gang
Starkenburg, Shawn R.
Waldo, Geoffrey
Banerjee, Shounak
Micheva‐Viteva, Sofiya N.
Nonclassical autophagy activation pathways are essential for production of infectious Influenza A virus in vitro
title Nonclassical autophagy activation pathways are essential for production of infectious Influenza A virus in vitro
title_full Nonclassical autophagy activation pathways are essential for production of infectious Influenza A virus in vitro
title_fullStr Nonclassical autophagy activation pathways are essential for production of infectious Influenza A virus in vitro
title_full_unstemmed Nonclassical autophagy activation pathways are essential for production of infectious Influenza A virus in vitro
title_short Nonclassical autophagy activation pathways are essential for production of infectious Influenza A virus in vitro
title_sort nonclassical autophagy activation pathways are essential for production of infectious influenza a virus in vitro
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9305535/
https://www.ncbi.nlm.nih.gov/pubmed/34931347
http://dx.doi.org/10.1111/mmi.14865
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