title: [Inhibition of hepatitis C virus replication by mycophenolic acid in hepatocytes].
abstract: OBJECTIVE
  It is well known that cyclosporine A (CsA), a widely used immunosuppressant for clinical organ transplantation, has the ability to inhibit HCV replication. In this study, the effects of several other immunosuppressants, including mycophenolic acid (MPA), rapamycin and FK-506, on HCV replication were examined in human hepatocytes.
  
  
  METHODS
  HCV JFH-l-infected hepatocytes were treated with immunosuppressants or with control vehicles. The levels of viral RNA and the expression of HCV core protein were determined by quantitative real-time RT-PCR and Western Blot assay, respectively.
  
  
  RESULTS
  MPA-treated cells showed significant decreases in both viral RNA and HCV Core protein expression compared with the control cells. Moreover, MPA treatments of hepatocytes before, during or after HCV infection could significantly inhibit viral replication. In contrast, rapamycin and FK-506 had little effect on HCV replication. Mechanism research disclosed that the inhibition of HCV replication by MPA was mainly due to its depletion of guanosine, a purine nucleoside crucial for synthesis of guanosine triphosphate (GTP), which is required for initiation of HCV RNA replication. The supplement of exogenous guanosine could reverse most of anti-HCV effect of MPA.
  
  
  CONCLUSIONS
  These results indicate that MPA, through the depletion of guanosine, inhibits HCV JFH-1 replication in hepatocytes, suggesting that MPA may be beneficial for HCV-infected transplant recipients.
authors.affiliation: Department of Geriatrics Digestion Internal Medicine, The first Affiliated Hospital of Guangxi Medical University, Guangxi 530021 ,China. haolphd@163.com
authors.forename: Hui
authors.initials: H
authors.lastname: Chen
authors.forename: Li
authors.initials: L
authors.lastname: Ye
authors.forename: Jin-ming
authors.initials: JM
authors.lastname: Su
authors.forename: Yu
authors.initials: Y
authors.lastname: Li
authors.forename: Jin-rong
authors.initials: JR
authors.lastname: Zeng
authors.forename: Wen-zhe
authors.initials: WZ
authors.lastname: Huo
mesh_terms: D045744:Cell Line, Tumor; D016174:Hepacivirus / Q000187:drug effects* / Q000235:genetics / Q000502:physiology*; D006526:Hepatitis C / Q000188:drug therapy / Q000821:virology*; D022781:Hepatocytes / Q000821:virology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D009173:Mycophenolic Acid / Q000494:pharmacology*; D012367:RNA, Viral / Q000235:genetics; D014779:Virus Replication / Q000187:drug effects* / Q000235:genetics
chemical_list: D007166:Immunosuppressive Agents; D012367:RNA, Viral; D009173:Mycophenolic Acid