Genomic Analysis of anti-HBV Activity by siRNA and Lamivudine in Stable HBV-producing Cell

We designed seven siRNAs based on the conserved HBV sequences and tested their effects on the expression of HBV genes following sorting of siRNA positive cells. Among these seven siRNAs, siRNA-1 and siRNA-7 were found to effectively suppress HBV gene expressions. We further addressed the global gene expression changes in stable HBV-producing cells induced by siRNA-1 and siRNA-7 using human genome-wide oligo microarrays. Data from the gene expression profilings indicated that siRNA-1 and siRNA-7 altered the expression of 54 and 499 genes, respectively, in HepG2.2.15 cells, which revealed the different siRNA had a varied pattern of gene expression profile and suggested complicated influence of siRNA on host cell. We further observed that eighteen of these genes were suppressed by both siRNA-1 and siRNA-7. Interestingly, seven of these genes were originally activated by HBV, which suggested these seven genes might be involved in the HBV-host cell interaction. Finally, we have compared the effects of siRNA and lamivudine on HBV and host cell, which revealed that siRNA is more effective in inhibiting the HBV expression at mRNA and protein level in vitro, and the gene expression profiling of HepG2.2.15 treated by lamivudine is totally different from siRNA¡¯s. Keywords: other siRNA vs. control lamivudine vs. mock