ArticleJournal of virology2014
Hepatitis C virus entry is impaired by claudin-1 downregulation in diacylglycerol acyltransferase-1-deficient cells.
Article in Journal of virology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
17 citing papers in PubMed, 31 citations in OpenAlex.
- Medicinal chemistry strategies toward host targeting antiviral agents.Medicinal research reviews · 2020Review
- Review
- Structure-based glycoengineering of interferon lambda 4 enhances its productivity and anti-viral potency.Cytokine · 2020Article
- Interferon-free treatment for hepatitis C virus infection induces normalization of extrahepatic type I interferon signaling.Clinical and molecular hepatology · 2018Article
- Suppression of Hepatitis C Virus Genome Replication and Particle Production by a Novel Diacylglycerol Acyltransferases Inhibitor.Molecules (Basel, Switzerland) · 2018Article
- Hepatitis C Virus Exploits Death Receptor 6-mediated Signaling Pathway to Facilitate Viral Propagation.Scientific reports · 2017Article
- CXCL10 is produced in hepatitis A virus-infected cells in an IRF3-dependent but IFN-independent manner.Scientific reports · 2017Article
- TALEN based HPV-E7 editing triggers necrotic cell death in cervical cancer cells.Scientific reports · 2017Article
- IFN-λ4 potently blocks IFN-α signalling by ISG15 and USP18 in hepatitis C virus infection.Scientific reports · 2017Article
- Structure, Function and Metabolism of Hepatic and Adipose Tissue Lipid Droplets: Implications in Alcoholic Liver Disease.Current molecular pharmacology · 2017Review
- Interferon-inducible protein SCOTIN interferes with HCV replication through the autolysosomal degradation of NS5A.Nature communications · 2016Article
- Prolonged silencing of diacylglycerol acyltransferase-1 induces a dedifferentiated phenotype in human liver cells.Journal of cellular and molecular medicine · 2016Article
- Modulation of host lipid metabolism by hepatitis C virus: Role of new therapies.World journal of gastroenterology · 2015Review
- Pim Kinase Interacts with Nonstructural 5A Protein and Regulates Hepatitis C Virus Entry.Journal of virology · 2015Article
- Roles of unphosphorylated ISGF3 in HCV infection and interferon responsiveness.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- Liver-targeted gene therapy: Approaches and challenges.Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society · 2015Review
- Lipids and RNA virus replication.Current opinion in virology · 2014Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 6 institutions in 2 countries.
Funding
Abstract
unlabelledDiacylglycerol acyltransferase-1 (DGAT1) is involved in the assembly of hepatitis C virus (HCV) by facilitating the trafficking of the HCV core protein to the lipid droplet. Here, we abrogated DGAT1 expression in Huh-7.5 cells by using either the transcription activator-like effector nuclease (TALEN) or lentivirus vector short hairpin RNA (shRNA) and achieved complete long-term silencing of DGAT1. HCV entry was severely impaired in DGAT1-silenced Huh-7.5 cell lines, which showed markedly diminished claudin-1 (CLDN1) expression. In DGAT1-silenced cell lines, the forced expression of CLDN1 restored HCV entry, implying that the downregulation of CLDN1 is a critical factor underlying defective HCV entry. The expression of the gene coding for hepatocyte nuclear factor 4α (HNF4α) and other hepatocyte-specific genes was also reduced in DGAT1-silenced cell lines. After DGAT1 gene rescue, CLDN1 expression was preserved, and HCV entry was restored. Strikingly, after DGAT1 silencing, CLDN1 expression and HCV entry were also restored by low-dose palmitic acid treatment, indicating that the downregulation of CLDN1 was associated with altered fatty acid homeostasis in the absence of DGAT1. Our findings provide novel insight into the role of DGAT1 in the life cycle of HCV. IMPORTANCE: In this study, we report the novel effect of complete silencing of DGAT1 on the entry of HCV. DGAT1 was recently reported as a host factor of HCV, involved in the assembly of HCV by facilitating the trafficking of the HCV core protein to lipid droplets. We achieved complete and long-term silencing of DGAT1 by either TALEN or repeated transduction of lentivirus shRNA. We found that HCV entry was severely impaired in DGAT1-silenced cell lines. The impairment of HCV entry was caused by CLDN1 downregulation, and the expression of HNF4α and other hepatocyte-specific genes was also downregulated in DGAT1-silenced cell lines. Our results suggest new roles of DGAT1 in human liver-derived cells: maintaining intracellular lipid homeostasis and affecting HCV entry by modulating CLDN1 expression.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.