Targeting Metabolic Reprogramming by Influenza Infection for Therapeutic Intervention
Influenza is a worldwide health and financial burden posing a significant risk to the immune-compromised, obese, diabetic, elderly, and pediatric populations. We identified increases in glucose metabolism in the lungs of pediatric patients infected with respiratory pathogens. Using quantitative mass...
Ausführliche Beschreibung
Autor*in: |
Heather S. Smallwood [verfasserIn] Susu Duan [verfasserIn] Marie Morfouace [verfasserIn] Svetlana Rezinciuc [verfasserIn] Barry L. Shulkin [verfasserIn] Anang Shelat [verfasserIn] Erika E. Zink [verfasserIn] Sandra Milasta [verfasserIn] Resha Bajracharya [verfasserIn] Ajayi J. Oluwaseum [verfasserIn] Martine F. Roussel [verfasserIn] Douglas R. Green [verfasserIn] Ljiljana Pasa-Tolic [verfasserIn] Paul G. Thomas [verfasserIn] |
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Format: |
E-Artikel |
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Sprache: |
Englisch |
Erschienen: |
2017 |
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Schlagwörter: |
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Übergeordnetes Werk: |
In: Cell Reports - Elsevier, 2015, 19(2017), 8, Seite 1640-1653 |
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Übergeordnetes Werk: |
volume:19 ; year:2017 ; number:8 ; pages:1640-1653 |
Links: |
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DOI / URN: |
10.1016/j.celrep.2017.04.039 |
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Katalog-ID: |
DOAJ013146092 |
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520 | |a Influenza is a worldwide health and financial burden posing a significant risk to the immune-compromised, obese, diabetic, elderly, and pediatric populations. We identified increases in glucose metabolism in the lungs of pediatric patients infected with respiratory pathogens. Using quantitative mass spectrometry, we found metabolic changes occurring after influenza infection in primary human respiratory cells and validated infection-associated increases in c-Myc, glycolysis, and glutaminolysis. We confirmed these findings with a metabolic drug screen that identified the PI3K/mTOR inhibitor BEZ235 as a regulator of infectious virus production. BEZ235 treatment ablated the transient induction of c-Myc, restored PI3K/mTOR pathway homeostasis measured by 4E-BP1 and p85 phosphorylation, and reversed infection-induced changes in metabolism. Importantly, BEZ235 reduced infectious progeny but had no effect on the early stages of viral replication. BEZ235 significantly increased survival in mice, while reducing viral titer. We show metabolic reprogramming of host cells by influenza virus exposes targets for therapeutic intervention. | ||
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700 | 0 | |a Barry L. Shulkin |e verfasserin |4 aut | |
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10.1016/j.celrep.2017.04.039 doi (DE-627)DOAJ013146092 (DE-599)DOAJ14d7ac117c7942c4a3b2b1bd69d18796 DE-627 ger DE-627 rakwb eng QH301-705.5 Heather S. Smallwood verfasserin aut Targeting Metabolic Reprogramming by Influenza Infection for Therapeutic Intervention 2017 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Influenza is a worldwide health and financial burden posing a significant risk to the immune-compromised, obese, diabetic, elderly, and pediatric populations. We identified increases in glucose metabolism in the lungs of pediatric patients infected with respiratory pathogens. Using quantitative mass spectrometry, we found metabolic changes occurring after influenza infection in primary human respiratory cells and validated infection-associated increases in c-Myc, glycolysis, and glutaminolysis. We confirmed these findings with a metabolic drug screen that identified the PI3K/mTOR inhibitor BEZ235 as a regulator of infectious virus production. BEZ235 treatment ablated the transient induction of c-Myc, restored PI3K/mTOR pathway homeostasis measured by 4E-BP1 and p85 phosphorylation, and reversed infection-induced changes in metabolism. Importantly, BEZ235 reduced infectious progeny but had no effect on the early stages of viral replication. BEZ235 significantly increased survival in mice, while reducing viral titer. We show metabolic reprogramming of host cells by influenza virus exposes targets for therapeutic intervention. metabolism influenza PET scan proteomics respiratory viral virus infection BEZ235 Biology (General) Susu Duan verfasserin aut Marie Morfouace verfasserin aut Svetlana Rezinciuc verfasserin aut Barry L. Shulkin verfasserin aut Anang Shelat verfasserin aut Erika E. Zink verfasserin aut Sandra Milasta verfasserin aut Resha Bajracharya verfasserin aut Ajayi J. Oluwaseum verfasserin aut Martine F. Roussel verfasserin aut Douglas R. Green verfasserin aut Ljiljana Pasa-Tolic verfasserin aut Paul G. Thomas verfasserin aut In Cell Reports Elsevier, 2015 19(2017), 8, Seite 1640-1653 (DE-627)684964562 (DE-600)2649101-1 22111247 nnns volume:19 year:2017 number:8 pages:1640-1653 https://doi.org/10.1016/j.celrep.2017.04.039 kostenfrei https://doaj.org/article/14d7ac117c7942c4a3b2b1bd69d18796 kostenfrei http://www.sciencedirect.com/science/article/pii/S2211124717305338 kostenfrei https://doaj.org/toc/2211-1247 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2110 GBV_ILN_2112 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 19 2017 8 1640-1653 |
spelling |
10.1016/j.celrep.2017.04.039 doi (DE-627)DOAJ013146092 (DE-599)DOAJ14d7ac117c7942c4a3b2b1bd69d18796 DE-627 ger DE-627 rakwb eng QH301-705.5 Heather S. Smallwood verfasserin aut Targeting Metabolic Reprogramming by Influenza Infection for Therapeutic Intervention 2017 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Influenza is a worldwide health and financial burden posing a significant risk to the immune-compromised, obese, diabetic, elderly, and pediatric populations. We identified increases in glucose metabolism in the lungs of pediatric patients infected with respiratory pathogens. Using quantitative mass spectrometry, we found metabolic changes occurring after influenza infection in primary human respiratory cells and validated infection-associated increases in c-Myc, glycolysis, and glutaminolysis. We confirmed these findings with a metabolic drug screen that identified the PI3K/mTOR inhibitor BEZ235 as a regulator of infectious virus production. BEZ235 treatment ablated the transient induction of c-Myc, restored PI3K/mTOR pathway homeostasis measured by 4E-BP1 and p85 phosphorylation, and reversed infection-induced changes in metabolism. Importantly, BEZ235 reduced infectious progeny but had no effect on the early stages of viral replication. BEZ235 significantly increased survival in mice, while reducing viral titer. We show metabolic reprogramming of host cells by influenza virus exposes targets for therapeutic intervention. metabolism influenza PET scan proteomics respiratory viral virus infection BEZ235 Biology (General) Susu Duan verfasserin aut Marie Morfouace verfasserin aut Svetlana Rezinciuc verfasserin aut Barry L. Shulkin verfasserin aut Anang Shelat verfasserin aut Erika E. Zink verfasserin aut Sandra Milasta verfasserin aut Resha Bajracharya verfasserin aut Ajayi J. Oluwaseum verfasserin aut Martine F. Roussel verfasserin aut Douglas R. Green verfasserin aut Ljiljana Pasa-Tolic verfasserin aut Paul G. Thomas verfasserin aut In Cell Reports Elsevier, 2015 19(2017), 8, Seite 1640-1653 (DE-627)684964562 (DE-600)2649101-1 22111247 nnns volume:19 year:2017 number:8 pages:1640-1653 https://doi.org/10.1016/j.celrep.2017.04.039 kostenfrei https://doaj.org/article/14d7ac117c7942c4a3b2b1bd69d18796 kostenfrei http://www.sciencedirect.com/science/article/pii/S2211124717305338 kostenfrei https://doaj.org/toc/2211-1247 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2110 GBV_ILN_2112 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 19 2017 8 1640-1653 |
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10.1016/j.celrep.2017.04.039 doi (DE-627)DOAJ013146092 (DE-599)DOAJ14d7ac117c7942c4a3b2b1bd69d18796 DE-627 ger DE-627 rakwb eng QH301-705.5 Heather S. Smallwood verfasserin aut Targeting Metabolic Reprogramming by Influenza Infection for Therapeutic Intervention 2017 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Influenza is a worldwide health and financial burden posing a significant risk to the immune-compromised, obese, diabetic, elderly, and pediatric populations. We identified increases in glucose metabolism in the lungs of pediatric patients infected with respiratory pathogens. Using quantitative mass spectrometry, we found metabolic changes occurring after influenza infection in primary human respiratory cells and validated infection-associated increases in c-Myc, glycolysis, and glutaminolysis. We confirmed these findings with a metabolic drug screen that identified the PI3K/mTOR inhibitor BEZ235 as a regulator of infectious virus production. BEZ235 treatment ablated the transient induction of c-Myc, restored PI3K/mTOR pathway homeostasis measured by 4E-BP1 and p85 phosphorylation, and reversed infection-induced changes in metabolism. Importantly, BEZ235 reduced infectious progeny but had no effect on the early stages of viral replication. BEZ235 significantly increased survival in mice, while reducing viral titer. We show metabolic reprogramming of host cells by influenza virus exposes targets for therapeutic intervention. metabolism influenza PET scan proteomics respiratory viral virus infection BEZ235 Biology (General) Susu Duan verfasserin aut Marie Morfouace verfasserin aut Svetlana Rezinciuc verfasserin aut Barry L. Shulkin verfasserin aut Anang Shelat verfasserin aut Erika E. Zink verfasserin aut Sandra Milasta verfasserin aut Resha Bajracharya verfasserin aut Ajayi J. Oluwaseum verfasserin aut Martine F. Roussel verfasserin aut Douglas R. Green verfasserin aut Ljiljana Pasa-Tolic verfasserin aut Paul G. Thomas verfasserin aut In Cell Reports Elsevier, 2015 19(2017), 8, Seite 1640-1653 (DE-627)684964562 (DE-600)2649101-1 22111247 nnns volume:19 year:2017 number:8 pages:1640-1653 https://doi.org/10.1016/j.celrep.2017.04.039 kostenfrei https://doaj.org/article/14d7ac117c7942c4a3b2b1bd69d18796 kostenfrei http://www.sciencedirect.com/science/article/pii/S2211124717305338 kostenfrei https://doaj.org/toc/2211-1247 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2110 GBV_ILN_2112 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 19 2017 8 1640-1653 |
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10.1016/j.celrep.2017.04.039 doi (DE-627)DOAJ013146092 (DE-599)DOAJ14d7ac117c7942c4a3b2b1bd69d18796 DE-627 ger DE-627 rakwb eng QH301-705.5 Heather S. Smallwood verfasserin aut Targeting Metabolic Reprogramming by Influenza Infection for Therapeutic Intervention 2017 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Influenza is a worldwide health and financial burden posing a significant risk to the immune-compromised, obese, diabetic, elderly, and pediatric populations. We identified increases in glucose metabolism in the lungs of pediatric patients infected with respiratory pathogens. Using quantitative mass spectrometry, we found metabolic changes occurring after influenza infection in primary human respiratory cells and validated infection-associated increases in c-Myc, glycolysis, and glutaminolysis. We confirmed these findings with a metabolic drug screen that identified the PI3K/mTOR inhibitor BEZ235 as a regulator of infectious virus production. BEZ235 treatment ablated the transient induction of c-Myc, restored PI3K/mTOR pathway homeostasis measured by 4E-BP1 and p85 phosphorylation, and reversed infection-induced changes in metabolism. Importantly, BEZ235 reduced infectious progeny but had no effect on the early stages of viral replication. BEZ235 significantly increased survival in mice, while reducing viral titer. We show metabolic reprogramming of host cells by influenza virus exposes targets for therapeutic intervention. metabolism influenza PET scan proteomics respiratory viral virus infection BEZ235 Biology (General) Susu Duan verfasserin aut Marie Morfouace verfasserin aut Svetlana Rezinciuc verfasserin aut Barry L. Shulkin verfasserin aut Anang Shelat verfasserin aut Erika E. Zink verfasserin aut Sandra Milasta verfasserin aut Resha Bajracharya verfasserin aut Ajayi J. Oluwaseum verfasserin aut Martine F. Roussel verfasserin aut Douglas R. Green verfasserin aut Ljiljana Pasa-Tolic verfasserin aut Paul G. Thomas verfasserin aut In Cell Reports Elsevier, 2015 19(2017), 8, Seite 1640-1653 (DE-627)684964562 (DE-600)2649101-1 22111247 nnns volume:19 year:2017 number:8 pages:1640-1653 https://doi.org/10.1016/j.celrep.2017.04.039 kostenfrei https://doaj.org/article/14d7ac117c7942c4a3b2b1bd69d18796 kostenfrei http://www.sciencedirect.com/science/article/pii/S2211124717305338 kostenfrei https://doaj.org/toc/2211-1247 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2110 GBV_ILN_2112 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 19 2017 8 1640-1653 |
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10.1016/j.celrep.2017.04.039 doi (DE-627)DOAJ013146092 (DE-599)DOAJ14d7ac117c7942c4a3b2b1bd69d18796 DE-627 ger DE-627 rakwb eng QH301-705.5 Heather S. Smallwood verfasserin aut Targeting Metabolic Reprogramming by Influenza Infection for Therapeutic Intervention 2017 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Influenza is a worldwide health and financial burden posing a significant risk to the immune-compromised, obese, diabetic, elderly, and pediatric populations. We identified increases in glucose metabolism in the lungs of pediatric patients infected with respiratory pathogens. Using quantitative mass spectrometry, we found metabolic changes occurring after influenza infection in primary human respiratory cells and validated infection-associated increases in c-Myc, glycolysis, and glutaminolysis. We confirmed these findings with a metabolic drug screen that identified the PI3K/mTOR inhibitor BEZ235 as a regulator of infectious virus production. BEZ235 treatment ablated the transient induction of c-Myc, restored PI3K/mTOR pathway homeostasis measured by 4E-BP1 and p85 phosphorylation, and reversed infection-induced changes in metabolism. Importantly, BEZ235 reduced infectious progeny but had no effect on the early stages of viral replication. BEZ235 significantly increased survival in mice, while reducing viral titer. We show metabolic reprogramming of host cells by influenza virus exposes targets for therapeutic intervention. metabolism influenza PET scan proteomics respiratory viral virus infection BEZ235 Biology (General) Susu Duan verfasserin aut Marie Morfouace verfasserin aut Svetlana Rezinciuc verfasserin aut Barry L. Shulkin verfasserin aut Anang Shelat verfasserin aut Erika E. Zink verfasserin aut Sandra Milasta verfasserin aut Resha Bajracharya verfasserin aut Ajayi J. Oluwaseum verfasserin aut Martine F. Roussel verfasserin aut Douglas R. Green verfasserin aut Ljiljana Pasa-Tolic verfasserin aut Paul G. Thomas verfasserin aut In Cell Reports Elsevier, 2015 19(2017), 8, Seite 1640-1653 (DE-627)684964562 (DE-600)2649101-1 22111247 nnns volume:19 year:2017 number:8 pages:1640-1653 https://doi.org/10.1016/j.celrep.2017.04.039 kostenfrei https://doaj.org/article/14d7ac117c7942c4a3b2b1bd69d18796 kostenfrei http://www.sciencedirect.com/science/article/pii/S2211124717305338 kostenfrei https://doaj.org/toc/2211-1247 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2110 GBV_ILN_2112 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 19 2017 8 1640-1653 |
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Heather S. Smallwood @@aut@@ Susu Duan @@aut@@ Marie Morfouace @@aut@@ Svetlana Rezinciuc @@aut@@ Barry L. Shulkin @@aut@@ Anang Shelat @@aut@@ Erika E. Zink @@aut@@ Sandra Milasta @@aut@@ Resha Bajracharya @@aut@@ Ajayi J. Oluwaseum @@aut@@ Martine F. Roussel @@aut@@ Douglas R. Green @@aut@@ Ljiljana Pasa-Tolic @@aut@@ Paul G. Thomas @@aut@@ |
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Heather S. Smallwood Susu Duan Marie Morfouace Svetlana Rezinciuc Barry L. Shulkin Anang Shelat Erika E. Zink Sandra Milasta Resha Bajracharya Ajayi J. Oluwaseum Martine F. Roussel Douglas R. Green Ljiljana Pasa-Tolic Paul G. Thomas |
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Targeting Metabolic Reprogramming by Influenza Infection for Therapeutic Intervention |
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Influenza is a worldwide health and financial burden posing a significant risk to the immune-compromised, obese, diabetic, elderly, and pediatric populations. We identified increases in glucose metabolism in the lungs of pediatric patients infected with respiratory pathogens. Using quantitative mass spectrometry, we found metabolic changes occurring after influenza infection in primary human respiratory cells and validated infection-associated increases in c-Myc, glycolysis, and glutaminolysis. We confirmed these findings with a metabolic drug screen that identified the PI3K/mTOR inhibitor BEZ235 as a regulator of infectious virus production. BEZ235 treatment ablated the transient induction of c-Myc, restored PI3K/mTOR pathway homeostasis measured by 4E-BP1 and p85 phosphorylation, and reversed infection-induced changes in metabolism. Importantly, BEZ235 reduced infectious progeny but had no effect on the early stages of viral replication. BEZ235 significantly increased survival in mice, while reducing viral titer. We show metabolic reprogramming of host cells by influenza virus exposes targets for therapeutic intervention. |
abstractGer |
Influenza is a worldwide health and financial burden posing a significant risk to the immune-compromised, obese, diabetic, elderly, and pediatric populations. We identified increases in glucose metabolism in the lungs of pediatric patients infected with respiratory pathogens. Using quantitative mass spectrometry, we found metabolic changes occurring after influenza infection in primary human respiratory cells and validated infection-associated increases in c-Myc, glycolysis, and glutaminolysis. We confirmed these findings with a metabolic drug screen that identified the PI3K/mTOR inhibitor BEZ235 as a regulator of infectious virus production. BEZ235 treatment ablated the transient induction of c-Myc, restored PI3K/mTOR pathway homeostasis measured by 4E-BP1 and p85 phosphorylation, and reversed infection-induced changes in metabolism. Importantly, BEZ235 reduced infectious progeny but had no effect on the early stages of viral replication. BEZ235 significantly increased survival in mice, while reducing viral titer. We show metabolic reprogramming of host cells by influenza virus exposes targets for therapeutic intervention. |
abstract_unstemmed |
Influenza is a worldwide health and financial burden posing a significant risk to the immune-compromised, obese, diabetic, elderly, and pediatric populations. We identified increases in glucose metabolism in the lungs of pediatric patients infected with respiratory pathogens. Using quantitative mass spectrometry, we found metabolic changes occurring after influenza infection in primary human respiratory cells and validated infection-associated increases in c-Myc, glycolysis, and glutaminolysis. We confirmed these findings with a metabolic drug screen that identified the PI3K/mTOR inhibitor BEZ235 as a regulator of infectious virus production. BEZ235 treatment ablated the transient induction of c-Myc, restored PI3K/mTOR pathway homeostasis measured by 4E-BP1 and p85 phosphorylation, and reversed infection-induced changes in metabolism. Importantly, BEZ235 reduced infectious progeny but had no effect on the early stages of viral replication. BEZ235 significantly increased survival in mice, while reducing viral titer. We show metabolic reprogramming of host cells by influenza virus exposes targets for therapeutic intervention. |
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Targeting Metabolic Reprogramming by Influenza Infection for Therapeutic Intervention |
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