en The Full Length Hepatitis C Virus Polyprotein and Interactions with the Interferon-Beta Signalling Pathways in vitro Related Fields Related Fields مقاله کامل Full Length/Original Article Background: Hepatitis C is a global health problem. The exact mechanisms by which hepatitis C virus (HCV) can evade the host immune system have become controversial. Whether HCV polyproteins modulate IFN signalling pathways or HCV proteins are responsible for such a property is the subject of interest. Therefore, an efficient baculovirus delivery system was developed to introduce the whole genome of HCV1B minus 3’untranslated region (UTR) (HCV1BΔ3’UTR) into hepatoma cells. Methods: The whole genome of HCV genotype 1b was developed into hepatoma cells. Also, two replicon constructs were used in this research: a recombinant baculovirus containing the culture adapted sub-genomic replicon (FK5.1) derived from HCV genotype 1b, and a mutant form containing an inactivating mutation within the non-structural protein 5B (NS5B). Results: As expected, the baculovirus carrying the FK5.1 replicon induced the production of IFN-gamma as judged by the use of an IFN- gamma promoter luciferase reporter construct, whereas the GND baculovirus (a control polymerase knock-out replicon) and the full-length 3’UTR deletant failed to induce luciferase expression. The activation of both IFN regulatory factor 3 (IRF3) and nuclear factor κB (NFκB), two transcription factors induced by dsRNA signalling were examined. Both the wild type and GND-mutant replicon blocked the dsRNA-induced activation of IRF3 and NFκB. Conclusion: Inhibition of the transcriptional response to IRF3 and NFκB seems to be one of the multiple mechanisms which HCV employs to escape the host immune defence. In contrast, the full length 3’UTR deletant had no significant effect on either transcription factor. These results may be attributed to the function of HCV subgenomic replicons when compared with full length 3’UTR deletant. Hepatitis C virus (HCV), IFN-β , IFN regulatory factor 3 (IRF3), Nuclear factor κ B (NFκ B) 23 34 http://ibj.pasteur.ac.ir/browse.php?a_code=A-10-1-71&slc_lang=en&sid=1 Masoud Sabouri Ghannad مسعود صبوری قناد sabouri39@yahoo.com Yes Alireza Zamani علیرضا زمانی No