title: Impaired interferon type I signalling in the liver modulates the hepatic acute phase response in hepatitis C virus transgenic mice.
abstract: OBJECTIVE
  The immunomodulatory active hepatitis C virus (HCV) has been shown to interfere with antiviral interferon (IFN) type I functions. The aim of the study was to determine whether further basic innate immunologic functions are influenced by HCV.
  
  
  METHODS
  The acute phase response (APR) was induced in HCV transgenic (tg) mice and C57BL/6J control mice using lipopolysaccharide. Activation of transcription factors, mRNA expression and production of cytokines and acute phase proteins (APP) were determined. IFN type I and tumor necrosis factor (TNF) alpha signalling were investigated after polyI:C or TNF-alpha treatment.
  
  
  RESULTS
  HCV tg mice showed an attenuated APR: hepatic activation of nuclear factor kappa B (NFkappaB) and interferon-stimulated gene factor 3 (ISGF3), hepatic expression of interleukin (IL) 6, IL-10, and IFN-gamma mRNA, serum concentrations of IL-6 and IFN-gamma and production of type II acute phase proteins were reduced compared to wild-type mice. While no differences in NFkappaB activation could be detected after TNF-alpha injection, HCV tg mice showed reduced activation of ISGF3 and reduced transactivation of IFN target genes after polyI:C treatment.
  
  
  CONCLUSIONS
  Besides antiviral defence mechanisms, interruption of IFN type I signalling by HCV modulates the APR which is aimed at a variety of pathogens.
authors.affiliation: Department of Internal Medicine I, Center for Internal Medicine, University of Ulm, Albert-Einstein Allee 23, 89081 Ulm, Germany. mona.wegert@unikinik-ulm.de
authors.forename: Mona
authors.initials: M
authors.lastname: Wegert
authors.forename: Nicola
authors.initials: N
authors.lastname: La Monica
authors.forename: Marco
authors.initials: M
authors.lastname: Tripodi
authors.forename: Guido
authors.initials: G
authors.lastname: Adler
authors.forename: Nektarios
authors.initials: N
authors.lastname: Dikopoulos
mesh_terms: D000209:Acute-Phase Proteins / Q000378:metabolism; D000210:Acute-Phase Reaction / Q000235:genetics / Q000276:immunology / Q000503:physiopathology*; D000818:Animals; D001483:Base Sequence; D016207:Cytokines / Q000097:blood / Q000235:genetics; D017931:DNA Primers / Q000235:genetics; D005260:Female; D016174:Hepacivirus / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity*; D018936:Hepatitis C Antigens / Q000235:genetics; D007370:Interferon Type I / Q000502:physiology*; D050832:Interferon-Stimulated Gene Factor 3 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000633:toxicity; D008099:Liver / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D016328:NF-kappa B / Q000378:metabolism; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology; D014758:Viral Core Proteins / Q000235:genetics / Q000276:immunology
chemical_list: D000209:Acute-Phase Proteins; D016207:Cytokines; D017931:DNA Primers; D018936:Hepatitis C Antigens; D007370:Interferon Type I; D050832:Interferon-Stimulated Gene Factor 3; D008070:Lipopolysaccharides; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D014758:Viral Core Proteins