Hepatitis C Virus Entry Is Impaired by Claudin-1 Downregulation in Diacylglycerol Acyltransferase-1-Deficient Cells

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Diacylglycerol 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 4 alpha (HNF4 alpha) 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.
Publisher
AMER SOC MICROBIOLOGY
Issue Date
2014-08
Language
English
Article Type
Article
Keywords

HEPATOCYTE NUCLEAR FACTOR-4-ALPHA; LIPID DROPLETS; HEPG2 CELLS; 1 DGAT1; INFECTION; PROTEIN; IDENTIFICATION; RECEPTOR; BINDING; GENOME

Citation

JOURNAL OF VIROLOGY, v.88, no.16, pp.9233 - 9244

ISSN
0022-538X
DOI
10.1128/JVI.01428-14
URI
http://hdl.handle.net/10203/192363
Appears in Collection
MSE-Journal Papers(저널논문)
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