title: Modulation of HCV reinfection after orthotopic liver transplantation by fibroblast growth factor-2 and other non-interferon mediators.
abstract: In HCV infected individuals graft infection occurs shortly after orthotopic liver transplantation (OLT). We aimed to describe the composition of the inflammatory response at this time, how it affects the HCV replication cycle and identify novel proviral and antiviral factors.
  
  
  
  We used a Luminex assay to quantify 50 inflammatory mediators in sera before and shortly after OLT. In vitro grown HCV based on the JFH-1 isolate were used to characterise the effects of patient sera and individual mediators on HCV.
  
  
  
  Although the mediator composition is highly variable between individuals, sera drawn immediately post-OLT significantly enhance HCV infectivity compared with control sera from before OLT in about half of the cases. Among 27 non-interferon inflammatory mediators fibroblast growth factor (FGF)-2 stood out as it enhanced HCV RNA replication and release of infectious particles. The effect was concentration-dependent and detectable in dividing and non-dividing cells. Moreover, pharmacological inhibition of FGF-2 receptor signalling abrogated the enhancing effect of FGF-2 and inhibited HCV replication in the absence of serum FGF-2 suggesting that HCV replication is dependent on basal activation of the FGF-2 triggered signalling pathway. Finally, in individuals with chronic HCV infection with high viral load, serum FGF-2 was significantly higher compared with those with low viral load.
  
  
  
  Although no single mediator may account for this effect, serum shortly post-OLT enhances HCV infection. FGF-2 is a novel endogenous driver of HCV replication and a potential therapeutic target.
authors: Department of Gastroenterology, Hepatology and Endocrinology, Medizinische Hochschule Hannover, Hannover, Germany German Center for Infection Research (DZIF), Hannover, Germany Institute for Molecular Biology, Medizinische Hochschule Hannover, Hannover, Germany.
authors: Nguyen Dinh
authors: ND
authors: Van
authors: Institute of Transplant Immunology, IFB-Tx, Medizinische Hochschule Hannover, Hannover, Germany.
authors: Christine S
authors: CS
authors: Falk
authors: Department of Gastroenterology, Hepatology and Endocrinology, Medizinische Hochschule Hannover, Hannover, Germany.
authors: Lisa
authors: L
authors: Sandmann
authors: German Center for Infection Research (DZIF), Hannover, Germany Department of General, Visceral and Transplantation Surgery, Medizinische Hochschule Hannover, Hannover, Germany.
authors: Florian W R
authors: FW
authors: Vondran
authors: German Center for Infection Research (DZIF), Hannover, Germany Department of General, Visceral and Transplantation Surgery, Medizinische Hochschule Hannover, Hannover, Germany.
authors: Fabian
authors: F
authors: Helfritz
authors: Department of Gastroenterology, Hepatology and Endocrinology, Medizinische Hochschule Hannover, Hannover, Germany German Center for Infection Research (DZIF), Hannover, Germany.
authors: Heiner
authors: H
authors: Wedemeyer
authors: Department of Gastroenterology, Hepatology and Endocrinology, Medizinische Hochschule Hannover, Hannover, Germany German Center for Infection Research (DZIF), Hannover, Germany.
authors: Michael P
authors: MP
authors: Manns
authors: Department of Gastroenterology, Hepatology and Endocrinology, Medizinische Hochschule Hannover, Hannover, Germany German Center for Infection Research (DZIF), Hannover, Germany.
authors: Sandra
authors: S
authors: Ciesek
authors: Department of Gastroenterology, Hepatology and Endocrinology, Medizinische Hochschule Hannover, Hannover, Germany German Center for Infection Research (DZIF), Hannover, Germany Institute for Molecular Biology, Medizinische Hochschule Hannover, Hannover, Germany.
authors: Thomas
authors: T
authors: von Hahn
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D016022:Case-Control Studies; D018925:Chemokines / Q000097:blood; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000097:blood*; D006084:Graft Rejection; D016174:Hepacivirus / Q000302:isolation & purification*; D006526:Hepatitis C / Q000097:blood* / Q000175:diagnosis / Q000517:prevention & control; D019698:Hepatitis C, Chronic / Q000601:surgery; D006801:Humans; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D012008:Recurrence; D012189:Retrospective Studies
chemical_list: D015415:Biomarkers; D018925:Chemokines; D016222:Fibroblast Growth Factor 2; D002097:C-Reactive Protein
keywords: HCV; HEPATITIS C; LIVER TRANSPLANTATION