Navigation überspringen
Universitätsbibliothek Heidelberg
Status: Bibliographieeintrag

Verfügbarkeit
Standort: ---
Exemplare: ---
heiBIB
 Online-Ressource
Verfasst von:Kinast, Volker [VerfasserIn]   i
 Plociennikowska, Agnieszka [VerfasserIn]   i
 Anggakusuma [VerfasserIn]   i
 Bracht, Thilo [VerfasserIn]   i
 Todt, Daniel [VerfasserIn]   i
 Brown, Richard J. P. [VerfasserIn]   i
 Boldanova, Tujana [VerfasserIn]   i
 Zhang, Yudi [VerfasserIn]   i
 Brüggemann, Yannick [VerfasserIn]   i
 Friesland, Martina [VerfasserIn]   i
 Engelmann, Michael [VerfasserIn]   i
 Vieyres, Gabrielle [VerfasserIn]   i
 Broering, Ruth [VerfasserIn]   i
 Vondran, Florian W. R. [VerfasserIn]   i
 Heim, Markus H. [VerfasserIn]   i
 Sitek, Barbara [VerfasserIn]   i
 Bartenschlager, Ralf [VerfasserIn]   i
 Pietschmann, Thomas [VerfasserIn]   i
 Steinmann, Eike [VerfasserIn]   i
Titel:C19orf66 is an interferon-induced inhibitor of HCV replication that restricts formation of the viral replication organelle
Verf.angabe:Volker Kinast, Agnieszka Plociennikowska, Anggakusuma, Thilo Bracht, Daniel Todt, Richard J. P. Brown, Tujana Boldanova, Yudi Zhang, Yannick Brüggemann, Martina Friesland, Michael Engelmann, Gabrielle Vieyres, Ruth Broering, Florian W. R. Vondran, Markus H. Heim, Barbara Sitek, Ralf Bartenschlager, Thomas Pietschmann, Eike Steinmann
E-Jahr:2020
Jahr:12 April 2020
Umfang:10 S.
Illustrationen:Illustrationen
Fussnoten:Gesehen am 29.09.2020
Titel Quelle:Enthalten in: Journal of hepatology
Ort Quelle:Amsterdam [u.a.] : Elsevier Science, 1985
Jahr Quelle:2020
Band/Heft Quelle:73(2020), 3, Seite 549-558
ISSN Quelle:1600-0641
Abstract:Background & Aims - HCV is a positive-strand RNA virus that primarily infects human hepatocytes. Recent studies have reported that C19orf66 is expressed as an interferon (IFN)-stimulated gene; however, the intrinsic regulation of this gene within the liver as well as its antiviral effects against HCV remain elusive. - Methods - Expression of C19orf66 was quantified in both liver biopsies and primary human hepatocytes, with or without HCV infection. Mechanistic studies of the potent anti-HCV phenotype mediated by C19orf66 were conducted using state-of-the-art virological, biochemical and genetic approaches, as well as correlative light and electron microscopy and transcriptome and proteome analysis. - Results - Upregulation of C19orf66 mRNA was observed in both primary human hepatocytes upon HCV infection and in the livers of patients with chronic hepatitis C (CHC). In addition, pegIFNα/ribavirin therapy induced C19orf66 expression in patients with CHC. Transcriptomic profiling and whole cell proteomics of hepatoma cells ectopically expressing C19orf66 revealed no induction of other antiviral genes. Expression of C19orf66 restricted HCV infection, whereas CRIPSPR/Cas9 mediated knockout of C19orf66 attenuated IFN-mediated suppression of HCV replication. Co-immunoprecipitation followed by mass spectrometry identified a stress granule protein-dominated interactome of C19orf66. Studies with subgenomic HCV replicons and an expression system revealed that C19orf66 expression impairs HCV-induced elevation of phosphatidylinositol-4-phosphate, alters the morphology of the viral replication organelle (termed the membranous web) and thereby targets viral RNA replication. - Conclusion - C19orf66 is an IFN-stimulated gene, which is upregulated in hepatocytes within the first hours post IFN treatment or HCV infection in vivo. The encoded protein possesses specific antiviral activity against HCV and targets the formation of the membranous web. Our study identifies C19orf66 as an IFN-inducible restriction factor with a novel antiviral mechanism that specifically targets HCV replication. - Lay summary - Interferon-stimulated genes are thought to be important to for antiviral immune responses to HCV. Herein, we analysed C19orf66, an interferon-stimulated gene, which appears to inhibit HCV replication. It prevents the HCV-induced elevation of phosphatidylinositol-4-phosphate and alters the morphology of HCV's replication organelle.
DOI:doi:10.1016/j.jhep.2020.03.047
URL:Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.

Volltext: https://doi.org/10.1016/j.jhep.2020.03.047
 Volltext: http://www.sciencedirect.com/science/article/pii/S0168827820302099
 DOI: https://doi.org/10.1016/j.jhep.2020.03.047
Datenträger:Online-Ressource
Sprache:eng
Sach-SW:Antiviral activity
 C19orf66
 HCV
 Hepatitis C virus
 Interferon-stimulated genes
 Membranous web
K10plus-PPN:1733891463
Verknüpfungen:→ Zeitschrift

Permanenter Link auf diesen Titel (bookmarkfähig):  https://katalog.ub.uni-heidelberg.de/titel/68641136   QR-Code
zum Seitenanfang