C19orf66 is an interferon-induced inhibitor of HCV replication that restricts formation of the viral replication organelle

  1. Kinast, Volker ORCID logo
  2. Plociennikowska, Agnieszka
  3. Anggakusuma
  4. Bracht, Thilo ORCID logo
  5. Todt, Daniel ORCID logo
  6. Brown, Richard ORCID logo
  7. Boldanova, Tujana
  8. Zhang, Yudi
  9. Brüggemann, Yannick ORCID logo
  10. Friesland, Martina
  11. Engelmann, Michael
  12. Vieyres, Gabrielle ORCID logo
  13. Broering, Ruth ORCID logo
  14. Vondran, Florian ORCID logo
  15. Heim, Markus H.
  16. Sitek, Barbara ORCID logo
  17. Bartenschlager, Ralf ORCID logo
  18. Pietschmann, Thomas ORCID logo
  19. Steinmann, Eike ORCID logo

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1000 Titel
  • C19orf66 is an interferon-induced inhibitor of HCV replication that restricts formation of the viral replication organelle
1000 Autor/in
  1. Kinast, Volker |
  2. Plociennikowska, Agnieszka |
  3. Anggakusuma |
  4. Bracht, Thilo |
  5. Todt, Daniel |
  6. Brown, Richard |
  7. Boldanova, Tujana |
  8. Zhang, Yudi |
  9. Brüggemann, Yannick |
  10. Friesland, Martina |
  11. Engelmann, Michael |
  12. Vieyres, Gabrielle |
  13. Broering, Ruth |
  14. Vondran, Florian |
  15. Heim, Markus H. |
  16. Sitek, Barbara |
  17. Bartenschlager, Ralf |
  18. Pietschmann, Thomas |
  19. Steinmann, Eike |
1000 Erscheinungsjahr 2020
1000 Publikationstyp
  1. Artikel |
1000 Online veröffentlicht
  • 2020-04-12
1000 Erschienen in
1000 Quellenangabe
  • 73(3):549-558
1000 FRL-Sammlung
1000 Copyrightjahr
  • 2020
1000 Lizenz
1000 Verlagsversion
  • https://doi.org/10.1016/j.jhep.2020.03.047 |
1000 Ergänzendes Material
  • https://www.journal-of-hepatology.eu/article/S0168-8278(20)30209-9/fulltext#supplementaryMaterial |
1000 Publikationsstatus
1000 Begutachtungsstatus
1000 Sprache der Publikation
1000 Abstract/Summary
  • BACKGROUND AND 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.
1000 Sacherschließung
lokal Antiviral activity
lokal Interferon-stimulated genes
lokal C19orf66
lokal Membranous web
lokal HCV
gnd 4262007-7 Hepatitis C
lokal Hepatitis C virus
1000 Fächerklassifikation (DDC)
1000 Liste der Beteiligten
  1. https://orcid.org/0000-0002-6984-678X|https://frl.publisso.de/adhoc/uri/IFBsb2NpZW5uaWtvd3NrYSwgQWduaWVzemthICAgIA==|https://frl.publisso.de/adhoc/uri/IEFuZ2dha3VzdW1hICAg|https://orcid.org/0000-0002-1194-6614|https://orcid.org/0000-0002-3564-1014|https://orcid.org/0000-0002-3292-6671|https://frl.publisso.de/adhoc/uri/IEJvbGRhbm92YSwgVHVqYW5hICA=|https://frl.publisso.de/adhoc/uri/ICAgWmhhbmcsIFl1ZGkgICA=|https://orcid.org/0000-0002-8790-0022|https://frl.publisso.de/adhoc/uri/IEZyaWVzbGFuZCwgTWFydGluYSAgICA=|https://frl.publisso.de/adhoc/uri/RW5nZWxtYW5uLCBNaWNoYWVsIA==|https://orcid.org/0000-0001-8511-2164|https://orcid.org/0000-0002-7125-3246|https://orcid.org/0000-0001-8355-5017|https://d-nb.info/gnd/1089839715|https://orcid.org/0000-0002-3797-8358|https://orcid.org/0000-0001-5601-9307|https://orcid.org/0000-0001-6789-4422|https://orcid.org/0000-0002-8771-4262
1000 Label
1000 Förderer
  1. Helmholtz-Alberta Initiative |
  2. Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung |
  3. Deutsche Forschungsgemeinschaft |
1000 Fördernummer
  1. -
  2. 310030B_147089
  3. TRR179, TP9
1000 Förderprogramm
  1. Helmholtz-Alberta Initiative For Infectious Disease Research (HAI-IDR).
  2. -
  3. -
1000 Dateien
1000 Förderung
  1. 1000 joinedFunding-child
    1000 Förderer Helmholtz-Alberta Initiative |
    1000 Förderprogramm Helmholtz-Alberta Initiative For Infectious Disease Research (HAI-IDR).
    1000 Fördernummer -
  2. 1000 joinedFunding-child
    1000 Förderer Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung |
    1000 Förderprogramm -
    1000 Fördernummer 310030B_147089
  3. 1000 joinedFunding-child
    1000 Förderer Deutsche Forschungsgemeinschaft |
    1000 Förderprogramm -
    1000 Fördernummer TRR179, TP9
1000 Objektart article
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1000 @id frl:6432686.rdf
1000 Erstellt am 2022-03-30T09:42:11.786+0200
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