Virus genotype-dependent transcriptional alterations in lipid metabolism and inflammation pathways in the Hepatitis C virus-infected liver

• Verfasst von: D'Avigdor, William M. H. [VerfasserIn]
• Verfasst von: Budzinska, Magdalena A. [VerfasserIn]
• Verfasst von: Lee, M. [VerfasserIn]
• Verfasst von: Lam, R. [VerfasserIn]
• Verfasst von: Kench, J. [VerfasserIn]
• Verfasst von: Stapelberg, M. [VerfasserIn]
• Verfasst von: McLennan, S. V. [VerfasserIn]
• Verfasst von: Farrell, G. [VerfasserIn]
• Verfasst von: George, J. [VerfasserIn]
• Verfasst von: McCaughan, G. W. [VerfasserIn]
• Verfasst von: Tu, Thomas [VerfasserIn]
• Verfasst von: Shackel, N. A. [VerfasserIn]
• Titel: Virus genotype-dependent transcriptional alterations in lipid metabolism and inflammation pathways in the Hepatitis C virus-infected liver
• Verf.angabe: W. M. H. d’Avigdor, M. A. Budzinska, M. Lee, R. Lam, J. Kench, M. Stapelberg, S. V. McLennan, G. Farrell, J. George, G. W. McCaughan, T. Tu, N. A. Shackel
• E-Jahr: 2019
• Jahr: 22 July 2019
• Umfang: 12 S.
• Fussnoten: Gesehen am 18.12.2019
• Titel Quelle: Enthalten in: Scientific reports
• Ort Quelle: [London] : Macmillan Publishers Limited, part of Springer Nature, 2011
• Jahr Quelle: 2019
• Band/Heft Quelle: 9(2019) Artikel-Nummer 10596, 12 Seiten
• ISSN Quelle: 2045-2322
• DOI: doi:10.1038/s41598-019-46664-0
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 168594759X

Abstract

Despite advances in antiviral therapy, molecular drivers of Hepatitis C Virus (HCV)-related liver disease remain poorly characterised. Chronic infection with HCV genotypes (1 and 3) differ in presentation of liver steatosis and virological response to therapies, both to interferon and direct acting antivirals. To understand what drives these clinically important differences, liver expression profiles of patients with HCV Genotype 1 or 3 infection (n = 26 and 33), alcoholic liver disease (n = 8), and no liver disease (n = 10) were analysed using transcriptome-wide microarrays. In progressive liver disease, HCV genotype was the major contributor to altered liver gene expression with 2151 genes differentially expressed >1.5-fold between HCV Genotype 1 and 3. In contrast, only 6 genes were altered between the HCV genotypes in advanced liver disease. Induction of lipogenic, lipolytic, and interferon stimulated gene pathways were enriched in Genotype 1 injury whilst a broad range of immune-associated pathways were associated with Genotype 3 injury. The results are consistent with greater lipid turnover in HCV Genotype 1 patients. Moreover, the lower activity in inflammatory pathways associated with HCV genotype 1 is consistent with relative resistance to interferon-based therapy. This data provides a molecular framework to explain the clinical manifestations of HCV-associated liver disease.