title: Divergent activities of interferon-alpha subtypes against intracellular hepatitis C virus replication.
abstract: BACKGROUND
  Interferon (IFN)-alpha is represented by several structurally related subtypes that show different antiviral and anti-tumor effects. Here, we analyzed differential effects of IFN-alpha subtypes on intracellular hepatitis C virus (HCV) replication using HCV subgenomic replicon system as a model.
  
  
  METHODS
  Huh7 and HeLa cells supporting expression of HCV replicon were treated with various concentrations of five recombinant human IFN-alpha subtypes 1, 2, 5, 8, and 10, and with IFN-alpha con1. The effects of IFNs on various cell-signaling pathways were assayed by using ISRE-, GAS-, AP1-, NF-kappa B-, CRE-, and SRE-luciferase reporter plasmids.
  
  
  RESULTS
  Each IFN-alpha subtype suppressed HCV replication in a dose-dependent manner. Among them, IFN-alpha8 was the most effective, while IFN-alpha1 was the least effective with 50% inhibitory concentrations of 0.123IU/ml versus 0.375IU/ml, respectively. These differential effects against HCV replication did not correlate with levels of the IFN-responsive ISRE or GAS reporter activities, nor they did activate the other reporters, AP1, NF-kappa B, CRE and SRE.
  
  
  CONCLUSIONS
  There were divergent effects of IFN-alpha subtypes against HCV replication that may be through JAK-STAT-independent pathways. Exploring further mechanisms of action may elucidate IFN-mediated cellular antiviral mechanisms.
authors.affiliation: Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyoku, Tokyo, Japan.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Koyama
authors.forename: Naoya
authors.initials: N
authors.lastname: Sakamoto
authors.forename: Yoko
authors.initials: Y
authors.lastname: Tanabe
authors.forename: Mina
authors.initials: M
authors.lastname: Nakagawa
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Itsui
authors.forename: Yoshie
authors.initials: Y
authors.lastname: Takeda
authors.forename: Sei
authors.initials: S
authors.lastname: Kakinuma
authors.forename: Yuko
authors.initials: Y
authors.lastname: Sekine
authors.forename: Shinya
authors.initials: S
authors.lastname: Maekawa
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Yanai
authors.forename: Masashi
authors.initials: M
authors.lastname: Kurimoto
authors.forename: Mamoru
authors.initials: M
authors.lastname: Watanabe