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Accession IconGSE84587

Expression data from primary human hepatocyte oxygenated co-cultures infected by HCV and human liver biopsies from HCV patients.

Organism Icon Homo sapiens
Sample Icon 9 Downloadable Samples
Technology Badge Icon Affymetrix Human Gene 1.0 ST Array (hugene10st), Affymetrix Human Genome U133A 2.0 Array (hgu133a2)

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Description
Viruses lack the basic machinery needed to replicate and therefore must hijack host metabolism to propagate. Virus-induced metabolic alterations have yet to be systematically studied in the context of the host transcriptional regulation, offering insight into host-pathogen metabolic interplay. In this work we identified Hepatitis C Virus (HCV)-responsive regulators by coupling system-wide metabolic flux analysis with targeted perturbation of nuclear receptors in primary human hepatocytes. We find HCV-induced up-regulation of glycolysis, ketogenesis and drug metabolism, controlled by activation of HNF4, PPAR, FXR and PXR, respectively. Pharmaceutical inhibition of HNF4 reversed HCV-induced glycolysis, blocking viral replication while increasing apoptosis in infected cells showing a viral-induced dependence on glycolysis. In contrast, pharmaceutical inhibition of PPAR or FXR reversed HCV-induced ketogenesis, but increased viral replication demonstrating a unique host anti-viral response. Our results show that viral-induced changes to host metabolism can be detrimental to its lifecycle demonstrating a distinct biological complexity.
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