Metabolic interference impairs influenza A virus replication by dampening vRNA synthesis
Abstract For replication, viruses exploit the host cell metabolism for biosynthesis of viral components. Recently, we could show that inhibition of glycolysis interfered with IAV replication by impairing the regulation of the viral polymerase as a transcriptase or replicase. Here, we investigated ho...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-03-01
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| Series: | npj Viruses |
| Online Access: | https://doi.org/10.1038/s44298-025-00090-4 |
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| author | Jens Kleinehr Chiara Robin Bojarzyn Michael Schöfbänker Katharina Daniel Stephan Ludwig Eike R. Hrincius |
| author_facet | Jens Kleinehr Chiara Robin Bojarzyn Michael Schöfbänker Katharina Daniel Stephan Ludwig Eike R. Hrincius |
| author_sort | Jens Kleinehr |
| collection | DOAJ |
| description | Abstract For replication, viruses exploit the host cell metabolism for biosynthesis of viral components. Recently, we could show that inhibition of glycolysis interfered with IAV replication by impairing the regulation of the viral polymerase as a transcriptase or replicase. Here, we investigated how IAV replication and polymerase regulation is influenced by other metabolic pathways which are directly or indirectly linked to glycolysis. Therefore, we inhibited glutaminolysis, fatty acid synthesis (FAS), oxidative phosphorylation (OXPHOS), and the pentose phosphate pathway (PPP). Inhibition of these metabolic pathways led to a significant reduction of viral titers. Furthermore, the inhibition of glutaminolysis, FAS and OXPHOS unbalanced the cellular glycolysis and respiration network leading to a prolonged phase of viral transcription while replication was strongly decreased. Our data indicate that affecting the cellular glycolysis and respiration balance impairs the dynamic regulation of the viral polymerase, resulting in reduced synthesis of viral genomic RNA and viral particles. |
| format | Article |
| id | doaj-art-7fe804f2cc75400d8e2e0ad4ed3945a4 |
| institution | OA Journals |
| issn | 2948-1767 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Viruses |
| spelling | doaj-art-7fe804f2cc75400d8e2e0ad4ed3945a42025-08-20T02:10:12ZengNature Portfolionpj Viruses2948-17672025-03-01311810.1038/s44298-025-00090-4Metabolic interference impairs influenza A virus replication by dampening vRNA synthesisJens Kleinehr0Chiara Robin Bojarzyn1Michael Schöfbänker2Katharina Daniel3Stephan Ludwig4Eike R. Hrincius5Institute of Virology Muenster (IVM), University of Muenster, Von-Esmarch-Straße 56Institute of Virology Muenster (IVM), University of Muenster, Von-Esmarch-Straße 56Institute of Virology Muenster (IVM), University of Muenster, Von-Esmarch-Straße 56Institute of Virology Muenster (IVM), University of Muenster, Von-Esmarch-Straße 56Institute of Virology Muenster (IVM), University of Muenster, Von-Esmarch-Straße 56Institute of Virology Muenster (IVM), University of Muenster, Von-Esmarch-Straße 56Abstract For replication, viruses exploit the host cell metabolism for biosynthesis of viral components. Recently, we could show that inhibition of glycolysis interfered with IAV replication by impairing the regulation of the viral polymerase as a transcriptase or replicase. Here, we investigated how IAV replication and polymerase regulation is influenced by other metabolic pathways which are directly or indirectly linked to glycolysis. Therefore, we inhibited glutaminolysis, fatty acid synthesis (FAS), oxidative phosphorylation (OXPHOS), and the pentose phosphate pathway (PPP). Inhibition of these metabolic pathways led to a significant reduction of viral titers. Furthermore, the inhibition of glutaminolysis, FAS and OXPHOS unbalanced the cellular glycolysis and respiration network leading to a prolonged phase of viral transcription while replication was strongly decreased. Our data indicate that affecting the cellular glycolysis and respiration balance impairs the dynamic regulation of the viral polymerase, resulting in reduced synthesis of viral genomic RNA and viral particles.https://doi.org/10.1038/s44298-025-00090-4 |
| spellingShingle | Jens Kleinehr Chiara Robin Bojarzyn Michael Schöfbänker Katharina Daniel Stephan Ludwig Eike R. Hrincius Metabolic interference impairs influenza A virus replication by dampening vRNA synthesis npj Viruses |
| title | Metabolic interference impairs influenza A virus replication by dampening vRNA synthesis |
| title_full | Metabolic interference impairs influenza A virus replication by dampening vRNA synthesis |
| title_fullStr | Metabolic interference impairs influenza A virus replication by dampening vRNA synthesis |
| title_full_unstemmed | Metabolic interference impairs influenza A virus replication by dampening vRNA synthesis |
| title_short | Metabolic interference impairs influenza A virus replication by dampening vRNA synthesis |
| title_sort | metabolic interference impairs influenza a virus replication by dampening vrna synthesis |
| url | https://doi.org/10.1038/s44298-025-00090-4 |
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