Hepatitis C virus enhances Rubicon expression, leading to autophagy inhibition and intracellular innate immune activation.
Animals
Autophagy
/ immunology
Autophagy-Related Proteins
/ immunology
Cell Line, Tumor
Cytoplasm
/ immunology
Hepacivirus
/ immunology
Hepatitis C, Chronic
/ immunology
Hepatocytes
/ immunology
Host-Pathogen Interactions
/ immunology
Humans
Immunity, Innate
/ immunology
Interferon Type I
/ immunology
Mice
Replicon
/ immunology
Signal Transduction
/ immunology
Virus Replication
/ immunology
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
17 09 2020
17 09 2020
Historique:
received:
11
06
2020
accepted:
18
08
2020
entrez:
18
9
2020
pubmed:
19
9
2020
medline:
15
12
2020
Statut:
epublish
Résumé
Autophagy, a degradation system, works to maintain cellular homeostasis. However, as the impact of Hepatitis C virus (HCV) infection on hepatocyte autophagy and its effect on HCV replication remain unclear, we examined them. HCV infection suppressed late-stage autophagy and increased Rubicon. siRNA-mediated knockdown of Rubicon promoted autophagy in HCV-infected cells. In Huh-7 cells harbouring the HCV replicon, Rubicon knockdown downregulated the expression of type 1 interferon (IFN)-related genes and upregulated HCV replication. Rubicon overexpression or administration of bafilomycin A1 or chloroquine, an inhibitor of late-stage autophagy, suppressed autophagy and activated the type 1 IFN pathway. On the other hand, Atg7 knockout suppressed early-stage autophagy and did not activate the type 1 IFN pathway. In livers of humanized liver chimeric mice, HCV infection increased Rubicon and enhanced type 1 IFN signalling. Elimination of HCV in the mice reduced the increase in Rubicon due to HCV infection. The expression levels of Rubicon and IFN-stimulated genes in chronic hepatitis C patients were higher than those in non-B, non-C hepatitis patients. HCV infection increased Rubicon and suppressed hepatocyte autophagy, leading to activation of the intracellular immune response. Rubicon induction is involved in HCV replication via activation of the intracellular immune response.
Identifiants
pubmed: 32943718
doi: 10.1038/s41598-020-72294-y
pii: 10.1038/s41598-020-72294-y
pmc: PMC7498609
doi:
Substances chimiques
Autophagy-Related Proteins
0
Interferon Type I
0
RUBCN protein, human
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
15290Références
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