Department of Microbiology, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran. Post code: 65178-3-8736.
Abstracts of the papers presented at the International Conference of Indian Virological Society on “Emerging and Re-emerging viral Diseases of the Tropics and Subtropics” at Indian Agricultural Research Institute, New Delhi, India, December 11–14, 2007.
In order to investigate the possible effects of HCV proteins on IFN-beta signalling, a baculovirus delivery system was developed to introduce the whole genome of HCV genotype 1b, into hepatoma cells. The construct used in this study lacked the 3’UTR which is required for HCV replication. Thus, it made possible to look at the effects of HCV proteins on the IFN-beta signalling pathway without inducing IFN-beta ex-pression by virtue of the presence of replicating (double-stranded) viral RNA. 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 NS5B (RdRp). As expected, the baculovirus carrying the FK5.1 replicon induced the production of IFN-beta as promoter luciferase reporter construct, whereas? judged by the use of an IFN- the GND baculovirus and the full-length 3’UTR deletant failed to induce luciferase ex-pression. The activation of both IRF-3 and NFêB, two transcription factors induced by dsRNA signalling that are key to the activation of transcription from the IFN-beta promoter was examined. Both the wildtype and GND-mutant replicon blocked the dsRNA-induced activation of IRF-3 and NFêB.
