Correlation of hepatitis C virus-mediated endoplasmic reticulum stress with autophagic flux impairment and hepatocarcinogenesis.
Autophagy
DNA damage
Endoplasmic reticulum stress
Hepatocellular carcinoma
Mallory-Denk body
Oxidative stress
Journal
Medical molecular morphology
ISSN: 1860-1499
Titre abrégé: Med Mol Morphol
Pays: Japan
ID NLM: 101239023
Informations de publication
Date de publication:
Jun 2021
Jun 2021
Historique:
received:
31
08
2020
accepted:
13
11
2020
pubmed:
3
1
2021
medline:
16
12
2021
entrez:
2
1
2021
Statut:
ppublish
Résumé
Hepatitis C virus (HCV) infection has been known to use autophagy for its replication. However, the mechanisms by which HCV modulates autophagy remain controversial. We used HCV-Japanese fulminant hepatitis-1-infected Huh7 cells. HCV infection induced the accumulation of autophagosomes. Morphological analyses of monomeric red fluorescent protein (mRFP)-green fluorescent protein (GFP) tandem fluorescent-tagged LC3 transfection showed HCV infection impaired autophagic flux. Autophagosome-lysosome fusion assessed by transfection of mRFP- or GFP-LC3 and immunostaining of lysosomal-associated membrane protein 1 was inhibited by HCV infection. Decrease of HCV-induced endoplasmic reticulum (ER) stress by 4-phenylbutyric acid, a chemical chaperone, improved the HCV-mediated autophagic flux impairment. HCV infection-induced oxidative stress and subsequently DNA damage, but not apoptosis. Furthermore, HCV induced cytoprotective effects against the cellular stress by facilitating the formation of cytoplasmic inclusion bodies as shown by p62 expression and by modulating keratin protein expression and activated nuclear factor erythroid 2-related factor 2. HCV eradication by direct-acting antivirals improved autophagic flux, but DNA damage persisted. In conclusion, HCV-induced ER stress correlates with autophagic flux impairment. Decrease of ER stress is considered to be a promising therapeutic strategy for HCV-related chronic liver diseases. However, we should be aware that the risk of hepatocarcinogenesis remains even after HCV eradication.
Identifiants
pubmed: 33386512
doi: 10.1007/s00795-020-00271-5
pii: 10.1007/s00795-020-00271-5
doi:
Substances chimiques
NF-E2-Related Factor 2
0
NFE2L2 protein, human
0
Keratins
68238-35-7
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
108-121Références
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