Host lipidome analysis during rhinovirus replication in HBECs identifies potential therapeutic targets

In patients with asthma or chronic obstructive pulmonary disease, rhinovirus (RV) 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 m...

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Bibliographic Details
Published in:Journal of lipid research Vol. 59; no. 9; pp. 1671 - 1684
Main Authors: Nguyen, An, Guedán, Anabel, Mousnier, Aurelie, Swieboda, Dawid, Zhang, Qifeng, Horkai, Dorottya, Le Novere, Nicolas, Solari, Roberto, Wakelam, Michael J O
Format: Journal Article
Language:English
Published: United States Elsevier 01.09.2018
Subjects:
Antiviral Agents - pharmacology
Bronchi - cytology
ceramidase
Epithelial Cells - metabolism
Epithelial Cells - virology
fatty acid synthase
HeLa Cells
human bronchial epithelial cells
Humans
Lipid Metabolism - drug effects
lipidomics
Molecular Targeted Therapy
Rhinovirus - drug effects
Rhinovirus - physiology
Virus Replication
ceramidase
human bronchial epithelial cells
fatty acid synthase
lipidomics
ISSN:1539-7262, 0022-2275, 1539-7262
Online Access:Get full text
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Summary:In patients with asthma or chronic obstructive pulmonary disease, rhinovirus (RV) 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 h period with the RV-A1b strain of RV 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 FA 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 FAS 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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ISSN:1539-7262
0022-2275
1539-7262
DOI:10.1194/jlr.M085910