title: IFN-Alpha receptor-1 upregulation in PBMC from HCV naïve patients carrying cc genotype. possible role of IFN-lambda.
abstract: OBJECTIVE
  IL-28B gene polymorphisms predict better therapeutic response and spontaneous clearance of HCV. Moreover, higher expression of IFN-lambda has been reported in patients with the rs12979860 CC favourable genotype. The study aim was to establish possible relationships between IL-28B rs12979860 genotypes and expression of IFN-alpha receptor-1 (IFNAR-1) in naïve HCV patients, and to explore the possible role of IFN-lambda.
  
  
  METHODS
  IFNAR-1 mRNA levels were measured in PBMC from naïve patients with chronic hepatitis C with different IL-28 genotypes. The ability of IFN-lambda to up-regulate the expression of IFNAR-1 was established in PBMC from healthy donors carrying different IL-28B genotypes.
  
  
  RESULTS
  Lower IFNAR-1 mRNA levels were observed in PBMC from HCV-infected naïve patients as compared to healthy donors. In healthy donors, IFNAR-1 mRNA levels were independent from IL-28B genotype, while in HCV patients, an increasing gradient was observed in TT vs CT vs CC carriers. In the latter group, a direct correlation between IFNAR-1 and endogenous IL-28B expression was observed. Moreover, IFN-lambda up-regulated IFNAR-1 expression in normal PBMC in a time-and dose-dependent manner, with a more effective response in CC vs TT carriers.
  
  
  CONCLUSIONS
  Endogenous levels of IFN-lambda may be responsible for partial restoration of IFNAR-1 expression in HCV patients with favourable IL-28 genotype. This, in turn, may confer to CC carriers a response advantage to either endogenous or exogenous IFN-alpha, representing the biological basis for the observed association between CC genotype and favourable outcome of either natural infection (clearance vs chronicization) or IFN therapy.
authors.affiliation: Laboratory of Virology, National Institute for Infectious Diseases "Lazzaro Spallanzani," Rome, Italy.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Lalle
authors.affiliation: Laboratory of Virology, National Institute for Infectious Diseases "Lazzaro Spallanzani," Rome, Italy.
authors.forename: Licia
authors.initials: L
authors.lastname: Bordi
authors.affiliation: Laboratory of Virology, National Institute for Infectious Diseases "Lazzaro Spallanzani," Rome, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Caglioti
authors.affiliation: Laboratory of Virology, National Institute for Infectious Diseases "Lazzaro Spallanzani," Rome, Italy.
authors.forename: Anna Rosa
authors.initials: AR
authors.lastname: Garbuglia
authors.affiliation: Laboratory of Virology, National Institute for Infectious Diseases "Lazzaro Spallanzani," Rome, Italy.
authors.forename: Concetta
authors.initials: C
authors.lastname: Castilletti
authors.affiliation: Clinical Department, National Institute for Infectious Diseases "Lazzaro Spallanzani," Rome, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Taibi
authors.affiliation: Clinical Department, National Institute for Infectious Diseases "Lazzaro Spallanzani," Rome, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Cristofari
authors.affiliation: Laboratory of Virology, National Institute for Infectious Diseases "Lazzaro Spallanzani," Rome, Italy.
authors.forename: Maria Rosaria
authors.initials: MR
authors.lastname: Capobianchi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000998:Antiviral Agents / Q000627:therapeutic use; D016022:Case-Control Studies; D005260:Female; D005786:Gene Expression Regulation; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics*; D006526:Hepatitis C / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000821:virology*; D006801:Humans; D007372:Interferons / Q000627:therapeutic use; D007378:Interleukins / Q000235:genetics*; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012333:RNA, Messenger / Q000235:genetics; D053633:Receptor, Interferon alpha-beta / Q000235:genetics*; D015854:Up-Regulation; D019562:Viral Load; D000095022:Interferon Lambda
chemical_list: D000998:Antiviral Agents; D007372:Interferons; D007378:Interleukins; D012333:RNA, Messenger; D053633:Receptor, Interferon alpha-beta; C000624353:interferon-lambda, human; D000095022:Interferon Lambda