Different activities of type I interferons on hepatitis B virus core promoter regulated transcription.
The type I interferons (IFNs) are a group of closely related cytokines which have different signal transduction pathways and different biological activities. Using transient transfection of human hepatoma cells with reporter plasmids containing the firefly/renilla luciferase genes under the control of the HBV-Enhancer (Enh) I, Enh II and core promoter we have investigated the biological activities of 10 recombinant (r) type I IFNs on transcription. Low concentrations of IFN (0.025 ng/ml) had a significant and specific inhibitory effect but the potencies of the different recombinant type I IFNs differed markedly with IFNalpha8 and IFNbeta being six-fold more potent than the least effective subtype (IFNalpha1). However, the addition of IFNalpha5-the subtype produced predominantly in the human liver-did not cause any synergistic effects.The non-natural consensus IFN displayed a more pronounced inhibition of HBV-regulated transcription than IFNalpha8 or IFNalpha2 but not IFNbeta. The INF-induced inhibitory effect was not dependent on the presence of the HBV-Enh1 and in particular of an interferon stimulated response element (ISRE)-like sequence. The characterization of different effects among type I interferons on HBV-regulatory elements may implicate an IFN-subtype-specific role for the pathogenesis and treatment of HBV-infection.
Schulte-Frohlinde
Ewert
E
Department of Medicine II of the Technical University of Munich, Germany. ewert.schulte-frohlinde@Irz.tu-muenchen.de
Seidler
Barbara
B
Burkard
Ines
I
Freilinger
Tobias
T
Lersch
Christian
C
Erfle
Volker
V
Foster
Graham R
GR
Classen
Meinhard
M
D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D015967:Gene Expression Regulation, Viral / Q000187:drug effects*; D017930:Genes, Reporter; D006515:Hepatitis B virus / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D007370:Interferon Type I / Q000494:pharmacology*; D011401:Promoter Regions, Genetic; D011994:Recombinant Proteins / Q000494:pharmacology; D014161:Transduction, Genetic
D007370:Interferon Type I; D011994:Recombinant Proteins