Host lipidome analysis during rhinovirus replication in human bronchial epithelial cells identifies potential therapeutic targets

An Nguyen, Anabel Guedan, Aurelie Mousnier, Dawid Swieboda, Qifeng Zhang, Dorottya Horkai, Nicolas Le Novere, Roberto Solari, Michael J O Wakelam

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Abstract

In patients with asthma or chronic obstructive pulmonary disease rhinovirus infections can provoke acute worsening of disease and limited treatment options exist. Viral replication in the host cell induces significant remodeling of intracellular membranes, but few studies have explored this mechanistically or as a therapeutic opportunity. We performed unbiased lipidomic analysis on human bronchial epithelial cells infected over a 6 hour period with the RV-A1b strain of rhinovirus to determine changes in 493 distinct lipid species. Through pathway and network analysis we identified temporal changes in the apparent activities of a number of lipid metabolizing and signaling enzymes. In particular, analysis highlighted fatty acid synthesis and ceramide metabolism as potential anti-rhinoviral targets. To validate the importance of these enzymes in viral replication, we explored the effects of commercially-available enzyme inhibitors upon RV-A1b infection and replication. Ceranib-1, D609 and C75 were the most potent inhibitors, which confirmed that fatty acid synthase and ceramidase are potential inhibitory targets in rhinoviral infections. More broadly, this study demonstrates the potential of lipidomics and pathway analysis to identify novel targets to treat human disorders.

Original languageEnglish
Pages (from-to)1671-1684
JournalJournal of Lipid Research
Volume59
Issue number9
Early online date26 Jun 2018
DOIs
Publication statusPublished - Sep 2018

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Rhinovirus
Ceramidases
Epithelial Cells
Lipids
Fatty Acid Synthases
Pulmonary diseases
Acid Ceramidase
Ceramides
Enzyme Inhibitors
Enzymes
Electric network analysis
Infection
Metabolism
Intracellular Membranes
Fatty Acids
Acute Disease
Membranes
Chronic Obstructive Pulmonary Disease
Therapeutics
Asthma

Cite this

Nguyen, An ; Guedan, Anabel ; Mousnier, Aurelie ; Swieboda, Dawid ; Zhang, Qifeng ; Horkai, Dorottya ; Le Novere, Nicolas ; Solari, Roberto ; Wakelam, Michael J O. / Host lipidome analysis during rhinovirus replication in human bronchial epithelial cells identifies potential therapeutic targets. In: Journal of Lipid Research. 2018 ; Vol. 59, No. 9. pp. 1671-1684.
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abstract = "In patients with asthma or chronic obstructive pulmonary disease rhinovirus infections can provoke acute worsening of disease and limited treatment options exist. Viral replication in the host cell induces significant remodeling of intracellular membranes, but few studies have explored this mechanistically or as a therapeutic opportunity. We performed unbiased lipidomic analysis on human bronchial epithelial cells infected over a 6 hour period with the RV-A1b strain of rhinovirus to determine changes in 493 distinct lipid species. Through pathway and network analysis we identified temporal changes in the apparent activities of a number of lipid metabolizing and signaling enzymes. In particular, analysis highlighted fatty acid synthesis and ceramide metabolism as potential anti-rhinoviral targets. To validate the importance of these enzymes in viral replication, we explored the effects of commercially-available enzyme inhibitors upon RV-A1b infection and replication. Ceranib-1, D609 and C75 were the most potent inhibitors, which confirmed that fatty acid synthase and ceramidase are potential inhibitory targets in rhinoviral infections. More broadly, this study demonstrates the potential of lipidomics and pathway analysis to identify novel targets to treat human disorders.",
author = "An Nguyen and Anabel Guedan and Aurelie Mousnier and Dawid Swieboda and Qifeng Zhang and Dorottya Horkai and {Le Novere}, Nicolas and Roberto Solari and Wakelam, {Michael J O}",
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Nguyen, A, Guedan, A, Mousnier, A, Swieboda, D, Zhang, Q, Horkai, D, Le Novere, N, Solari, R & Wakelam, MJO 2018, 'Host lipidome analysis during rhinovirus replication in human bronchial epithelial cells identifies potential therapeutic targets', Journal of Lipid Research, vol. 59, no. 9, pp. 1671-1684. https://doi.org/10.1194/jlr.M085910

Host lipidome analysis during rhinovirus replication in human bronchial epithelial cells identifies potential therapeutic targets. / Nguyen, An; Guedan, Anabel; Mousnier, Aurelie; Swieboda, Dawid; Zhang, Qifeng; Horkai, Dorottya; Le Novere, Nicolas; Solari, Roberto; Wakelam, Michael J O.

In: Journal of Lipid Research, Vol. 59, No. 9, 09.2018, p. 1671-1684.

Research output: Contribution to journalArticle

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T1 - Host lipidome analysis during rhinovirus replication in human bronchial epithelial cells identifies potential therapeutic targets

AU - Nguyen, An

AU - Guedan, Anabel

AU - Mousnier, Aurelie

AU - Swieboda, Dawid

AU - Zhang, Qifeng

AU - Horkai, Dorottya

AU - Le Novere, Nicolas

AU - Solari, Roberto

AU - Wakelam, Michael J O

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AB - In patients with asthma or chronic obstructive pulmonary disease rhinovirus infections can provoke acute worsening of disease and limited treatment options exist. Viral replication in the host cell induces significant remodeling of intracellular membranes, but few studies have explored this mechanistically or as a therapeutic opportunity. We performed unbiased lipidomic analysis on human bronchial epithelial cells infected over a 6 hour period with the RV-A1b strain of rhinovirus to determine changes in 493 distinct lipid species. Through pathway and network analysis we identified temporal changes in the apparent activities of a number of lipid metabolizing and signaling enzymes. In particular, analysis highlighted fatty acid synthesis and ceramide metabolism as potential anti-rhinoviral targets. To validate the importance of these enzymes in viral replication, we explored the effects of commercially-available enzyme inhibitors upon RV-A1b infection and replication. Ceranib-1, D609 and C75 were the most potent inhibitors, which confirmed that fatty acid synthase and ceramidase are potential inhibitory targets in rhinoviral infections. More broadly, this study demonstrates the potential of lipidomics and pathway analysis to identify novel targets to treat human disorders.

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