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  2. College of Medicine / 醫學院
  3. Biochemistry and Molecular Biology / 生物化學暨分子生物學研究所
  4. Hepatitis C virus replication is modulated by the interaction of nonstructural protein NS5B and fatty acid synthase
 
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Hepatitis C virus replication is modulated by the interaction of nonstructural protein NS5B and fatty acid synthase

Journal
Journal of Virology
Journal Volume
87
Journal Issue
9
Pages
4994-5004
Date Issued
2013
Author(s)
Huang J.-T.
Tseng C.-P.
Liao M.-H.
SHAO-CHUN LU 
Yeh W.-Z.
Sakamoto N.
Chen C.-M.
Cheng J.-C.
DOI
10.1128/JVI.02526-12
URI
https://www.scopus.com/inward/record.uri?eid=2-s2.0-84876315023&doi=10.1128%2fJVI.02526-12&partnerID=40&md5=f61296e767a3f1f1a2dc9d279bec7c26
https://scholars.lib.ntu.edu.tw/handle/123456789/454615
Abstract
Hepatitis C virus (HCV) nonstructural protein 5B (NS5B) is an RNA-dependent RNA polymerase (RdRp) that acts as a key player in the HCV replication complex. Understanding the interplay between the viral and cellular components of the HCV replication complex could provide new insight for prevention of the progression of HCV-associated hepatocellular carcinoma (HCC). In this study, the NS5B protein was used as the bait in a pulldown assay to screen for NS5B-interacting proteins that are present in Huh7 hepatoma cell lysates. After mass spectrophotometric analysis, fatty acid synthase (FASN) was found to interact with NS5B. Coimmunoprecipitation and double staining assays further confirmed the direct binding between NS5B and FASN. The domain of NS5B that interacts with FASN was also determined. Moreover, FASN was associated with detergent-resistant lipid rafts and colocalized with NS5B in active HCV replication complexes. In addition, overexpression of FASN enhanced HCV expression in Huh7/Rep-Feo cells, while transfection of FASN small interfering RNA (siRNA) or treatment with FASN-specific inhibitors decreased HCV replication and viral production. Notably, FASN directly increased HCV NS5B RdRp activity in vitro. These results together indicate that FASN interacts with NS5B and modulates HCV replication through a direct increase of NS5B RdRp activity. FASN may thereby serve as a target for the treatment of HCV infection and the prevention of HCV-associated HCC progression. ? 2013, American Society for Microbiology.
SDGs

[SDGs]SDG3

Other Subjects
fatty acid synthase; nonstructural protein 5B; RNA directed RNA polymerase; amino terminal sequence; article; binding affinity; binding site; cell lysate; controlled study; enzyme activity; enzyme assay; Hepatitis C virus; immunoprecipitation; in vitro study; lipid raft; mass spectrometry; matrix assisted laser desorption ionization time of flight mass spectrometry; nonhuman; priority journal; protein binding; protein determination; protein domain; protein expression; protein function; protein localization; protein protein interaction; proteomics; virus expression; virus replication; Cell Line, Tumor; Fatty Acid Synthetase Complex; Hepacivirus; Hepatitis C; Humans; Protein Binding; Viral Nonstructural Proteins; Virus Replication; Hepatitis C virus
Type
journal article

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