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

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Title
Hepatitis C Virus Entry Is Impaired by Claudin-1 Downregulation in Diacylglycerol Acyltransferase-1-Deficient Cells
Author(s)
Pil Soo Sung; Asako Murayama; Wonseok Kang; Myung-Sun Kim; Seung Kew Yoon; Masayoshi Fukasawa; Masuo Kondoh; Jin-Soo Kim; Hyongbum Kim; Takanobu Kato; Eui-Cheol Shin
Publication Date
2014-08
Journal
JOURNAL OF VIROLOGY, v.88, no.16, pp.9233 - 9244
Publisher
AMER SOC MICROBIOLOGY
Abstract
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 (HNF4) 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.
URI
https://pr.ibs.re.kr/handle/8788114/941
ISSN
0022-538X
Appears in Collections:
Center for Genome Engineering(유전체 교정 연구단) > Journal Papers (저널논문)
Files in This Item:
GEL_20140604_Hepatitis_C_VirusEntry_is_Impaired_by_Claudin-1_Downregulation.pdfDownload

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