Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
  • Clinical Research and Public Health
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Video Abstracts
  • Reviews
    • View all reviews ...
    • Pancreatic Cancer (Jul 2025)
    • Complement Biology and Therapeutics (May 2025)
    • Evolving insights into MASLD and MASH pathogenesis and treatment (Apr 2025)
    • Microbiome in Health and Disease (Feb 2025)
    • Substance Use Disorders (Oct 2024)
    • Clonal Hematopoiesis (Oct 2024)
    • Sex Differences in Medicine (Sep 2024)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Clinical Research and Public Health
    • Research Letters
    • Letters to the Editor
    • Editorials
    • Commentaries
    • Editor's notes
    • Reviews
    • Viewpoints
    • 100th anniversary
    • Top read articles

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Video Abstracts
  • In-Press Preview
  • Clinical Research and Public Health
  • Research Letters
  • Letters to the Editor
  • Editorials
  • Commentaries
  • Editor's notes
  • Reviews
  • Viewpoints
  • 100th anniversary
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
Activation of the unfolded protein response and autophagy after hepatitis C virus infection suppresses innate antiviral immunity in vitro
Po-Yuan Ke, Steve S.-L. Chen
Po-Yuan Ke, Steve S.-L. Chen
Published December 6, 2010
Citation Information: J Clin Invest. 2011;121(1):37-56. https://doi.org/10.1172/JCI41474.
View: Text | PDF
Research Article Virology Article has an altmetric score of 10

Activation of the unfolded protein response and autophagy after hepatitis C virus infection suppresses innate antiviral immunity in vitro

  • Text
  • PDF
Abstract

Autophagy, a process for catabolizing cytoplasmic components, has been implicated in the modulation of interactions between RNA viruses and their host. However, the mechanism underlying the functional role of autophagy in the viral life cycle still remains unclear. Hepatitis C virus (HCV) is a single-stranded, positive-sense, membrane-enveloped RNA virus that can cause chronic liver disease. Here we report that HCV induces the unfolded protein response (UPR), which in turn activates the autophagic pathway to promote HCV RNA replication in human hepatoma cells. Further analysis revealed that the entire autophagic process through to complete autolysosome maturation was required to promote HCV RNA replication and that it did so by suppressing innate antiviral immunity. Gene silencing or activation of the UPR-autophagy pathway activated or repressed, respectively, IFN-β activation mediated by an HCV-derived pathogen-associated molecular pattern (PAMP). Similar results were achieved with a PAMP derived from Dengue virus (DEV), indicating that HCV and DEV may both exploit the UPR-autophagy pathway to escape the innate immune response. Taken together, these results not only define the physiological significance of HCV-induced autophagy, but also shed light on the knowledge of host cellular responses upon HCV infection as well as on exploration of therapeutic targets for controlling HCV infection.

Authors

Po-Yuan Ke, Steve S.-L. Chen

×

Figure 10

Effect of CQ on rapamycin- and DTT-triggered autophagic process.

Options: View larger image (or click on image) Download as PowerPoint
Effect of CQ on rapamycin- and DTT-triggered autophagic process.
(A–C) H...
(A–C) Huh7/mRFP-GFP-LC3 cells were left untreated or treated with 4 mM rapamycin or 4 mM rapamycin in the presence (+) or absence (–) of 100 μM CQ. Six hours after treatment, cells were analyzed by Western blot analysis (A and B, left panels) and quantified for RFP-LC3–labeled (RFP-positive) and RFP-GFP-LC3–labeled (RFP-GFP-positive, yellow-colored) puncta structures by confocal microscopy (A and B, middle and right panels; scale bars: 10 μm). Another set of reporter cells was treated with drugs according to the procedure described above and fixed and analyzed by TEM for formation of autophagic vacuoles (C). The black arrowheads indicate the AVi or AVd, and the white arrows unAVd. Data represent mean ± SEM (n = 3) (A and B).

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts

Picked up by 1 news outlets
Referenced in 1 Wikipedia pages
166 readers on Mendeley
See more details