Initial HCV infection of adult hepatocytes triggers a temporally structured transcriptional program containing diverse pro- and anti-viral elements.


Journal

Journal of virology
ISSN: 1098-5514
Titre abrégé: J Virol
Pays: United States
ID NLM: 0113724

Informations de publication

Date de publication:
26 04 2021
Historique:
entrez: 4 3 2021
pubmed: 5 3 2021
medline: 5 3 2021
Statut: ppublish

Résumé

Transcriptional profiling provides global snapshots of virus-mediated cellular reprogramming, which can simultaneously encompass pro- and antiviral components. To determine early transcriptional signatures associated with HCV infection of authentic target cells, we performed ex vivo infections of adult primary human hepatocytes (PHHs) from seven donors. Longitudinal sampling identified minimal gene dysregulation at six hours post infection (hpi). In contrast, at 72 hpi, massive increases in the breadth and magnitude of HCV-induced gene dysregulation were apparent, affecting gene classes associated with diverse biological processes. Comparison with HCV-induced transcriptional dysregulation in Huh-7.5 cells identified limited overlap between the two systems. Of note, in PHHs, HCV infection initiated broad upregulation of canonical interferon (IFN)-mediated defense programs, limiting viral RNA replication and abrogating virion release. We further find that constitutive expression of

Identifiants

pubmed: 33658347
pii: JVI.00245-21
doi: 10.1128/JVI.00245-21
pmc: PMC8139656
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

Copyright © 2021 American Society for Microbiology.

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Auteurs

Birthe Tegtmeyer (B)

Institute of Experimental Virology, TWINCORE, Centre for Experimental and Clinical Infection Research; a joint venture between the Medical School Hannover (MHH) and the Helmholtz Centre for Infection Research (HZI), Hannover, Germany.

Gabrielle Vieyres (G)

Heinrich Pette Institute, Leibniz Institute for Experimental Virology, Hamburg, Germany.

Daniel Todt (D)

Department of Molecular and Medical Virology, Bochum, Germany.
European Virus Bioinformatics Center (EVBC), Jena, Germany.

Chris Lauber (C)

Institute of Experimental Virology, TWINCORE, Centre for Experimental and Clinical Infection Research; a joint venture between the Medical School Hannover (MHH) and the Helmholtz Centre for Infection Research (HZI), Hannover, Germany.

Corinne Ginkel (C)

Institute of Experimental Virology, TWINCORE, Centre for Experimental and Clinical Infection Research; a joint venture between the Medical School Hannover (MHH) and the Helmholtz Centre for Infection Research (HZI), Hannover, Germany.

Michael Engelmann (M)

Department of Molecular and Medical Virology, Bochum, Germany.

Maike Herrmann (M)

Division of Veterinary Medicine, Paul Ehrlich Institute, Langen, Germany.

Christian K Pfaller (CK)

Division of Veterinary Medicine, Paul Ehrlich Institute, Langen, Germany.

Florian W R Vondran (FWR)

Department of General, Visceral and Transplant Surgery, Hannover Medical School, Hannover, Germany; German Centre for Infection Research (DZIF), partner site Hannover-Braunschweig, Hannover, Germany.

Ruth Broering (R)

Department of Gastroenterology and Hepatology, University Hospital Essen, University Duisburg-Essen, Essen, Germany.

Ehsan Vafadarnejad (E)

Helmholtz Institute for RNA-based Infection Research (HIRI), Helmholtz Centre for Infection Research (HZI), Würzburg, Germany.

Antoine-Emmanuel Saliba (AE)

Helmholtz Institute for RNA-based Infection Research (HIRI), Helmholtz Centre for Infection Research (HZI), Würzburg, Germany.

Christina Puff (C)

Department of Pathology, University of Veterinary Medicine Hannover, Hannover, Germany.

Wolfgang Baumgärtner (W)

Department of Pathology, University of Veterinary Medicine Hannover, Hannover, Germany.

Csaba Miskey (C)

Division of Medical Biotechnology, Paul Ehrlich Institute, Langen, Germany.

Zoltán Ivics (Z)

Division of Medical Biotechnology, Paul Ehrlich Institute, Langen, Germany.

Eike Steinmann (E)

Department of Molecular and Medical Virology, Bochum, Germany.

Thomas Pietschmann (T)

Institute of Experimental Virology, TWINCORE, Centre for Experimental and Clinical Infection Research; a joint venture between the Medical School Hannover (MHH) and the Helmholtz Centre for Infection Research (HZI), Hannover, Germany.

Richard J P Brown (RJP)

Division of Veterinary Medicine, Paul Ehrlich Institute, Langen, Germany Richard.Brown@pei.de.

Classifications MeSH