title: The FUSE binding protein is a cellular factor required for efficient replication of hepatitis C virus.
abstract: Hepatitis C virus (HCV) infection is the leading cause of liver cirrhosis and hepatocellular carcinoma and one of the primary indications for liver transplantation. The molecular mechanisms underlying the actions of host factors in HCV replication remain poorly defined. FUSE (far upstream element of the c-myc proto-oncogene) binding protein (FBP) is a cellular factor that we have identified as a binder of HCV 3' nontranslated region (3'NTR). Mapping of the binding site showed that FBP specifically interacts with the poly(U) tract within the poly(U/UC) region of the 3'NTR. Silencing of FBP expression by small interfering RNA in cells carrying HCV subgenomic replicons severely reduced viral replication, while overexpression of FBP significantly enhanced viral replication. We confirmed these observations by an in vitro HCV replication assay in the cell-free replicative lysate, which suggested that there is a direct correlation between the cellular FBP level and HCV replication. FBP immunoprecipitation coprecipitated HCV nonstructural protein 5A (NS5A), indicating that FBP interacts with HCV NS5A, which is known to function as a link between HCV translation and replication. Although FBP is mainly localized in the nucleus, we found that in MH14 cells a significant level of this protein is colocalized with NS5A in the cytosol, a site of HCV replication. While the mechanism of FBP involvement in HCV replication is yet to be delineated, our findings suggest that it may be an important regulatory component that is essential for efficient replication of HCV.
authors.affiliation: Department of Biochemistry and Molecular Biology, UMDNJ-New Jersey Medical School, 185 South Orange Avenue, Newark, NJ 07103, USA.
authors.forename: Zhengbin
authors.initials: Z
authors.lastname: Zhang
authors.forename: Dylan
authors.initials: D
authors.lastname: Harris
authors.forename: Virendra N
authors.initials: VN
authors.lastname: Pandey
mesh_terms: D001665:Binding Sites; D002352:Carrier Proteins / Q000378:metabolism / Q000502:physiology*; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D002474:Cell-Free System; D003432:Cross-Linking Reagents / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D019085:Fluorescent Antibody Technique, Direct; D015967:Gene Expression Regulation, Viral; D017930:Genes, Reporter; D016174:Hepacivirus / Q000235:genetics / Q000502:physiology*; D006801:Humans; D008156:Luciferases / Q000032:analysis / Q000378:metabolism; D009841:Oligonucleotides / Q000378:metabolism; D010957:Plasmids; D011485:Protein Binding; D000090063:Proto-Oncogene Mas; D034741:RNA, Small Interfering / Q000378:metabolism; D012367:RNA, Viral / Q000032:analysis; D012093:Replicon; D014162:Transfection; D017361:Viral Nonstructural Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D014779:Virus Replication
chemical_list: D002352:Carrier Proteins; D003432:Cross-Linking Reagents; C000715470:MAS1 protein, human; D009841:Oligonucleotides; D000090063:Proto-Oncogene Mas; D034741:RNA, Small Interfering; D012367:RNA, Viral; D017361:Viral Nonstructural Proteins; D008156:Luciferases