CC variant has been associated with non response to the IFN therapy and with lower rates of spontaneous clearance of HCV infection. The poor response variant is also associated with higher intrahe patic expression level of ISGs. A missing aspect in this scenario is the study of the effect produced by HCV on the expression of IFN b induced miRs. This is a relevant issue Idelalisib 870281-82-6 to understand how the virus can suppress the innate antiviral signaling and induce a persistent infection. In a previous paper, we identified a common transcrip tional response of Huh 7 cells to different clones of full length HCV replicon. Although a more advanced HCV cell culture models that release HCV viral particles has been developed, the replicon system has the advantage of taking into account the cellular gene expres sion variability of different HCV Inhibitors,Modulators,Libraries replicon cell clones.
This approach allows searching for modulated genes shared by all clones, which are likely to be strictly needed for viral replication in different cellular contexts. On this basis, we used the replicon system to identify IFN regulated miRs that are Inhibitors,Modulators,Libraries Inhibitors,Modulators,Libraries modulated by HCV RNA replication. In particular, we analyzed the expression profile of 24 selected miRs in IFN b treated Huh 7 cell line and in three cell clones carrying a full length HCV replicon. Among the identi fied 16 miRs modulated in the 21 5 clone, 3 miRs showed concordant expression when analyzed in the two other HCV replicons. By a combined approach, based on bioinformatic prediction and microarray analy sis, we also identified 37 genes, targeted by the 3 miRs, which are involved in pathways and biological processes potentially implicated in the control of antiviral response by HCV infection.
Results Expression of IFN b regulated miRs in 21 5 HCV replicon cells and in IFN b treated Huh 7 cells To determine the impact of HCV RNA replication and protein synthesis on IFN b regulated miRs, we com pared the expression profile of selected miRs in 21 5 cells, Inhibitors,Modulators,Libraries harbouring a full length HCV genome, and in IFN b treated Huh 7 cells with the Huh 7 parental cell line. In particular, the list of assayed miRs includes eight IFN b induced miRs, which Carfilzomib displayed complementarity in their seed sequences with HCV RNA genome, two miRs reported as IFN b unre sponsive miRs, miR 122a that promotes HCV RNA replication and three miRs modulated in innate immune response in monocytes macrophages.
Actually, the name of five of the above miRs indi cates miR families, not just individual mature miR spe cies, thus, we analysed find FAQ the level of each member of those families. Overall, the expression profile of 24 miRs in 21 5 and IFN b treated Huh 7 cell lines was analysed. Three miRs showed an expression level below the detection limit of the assay, while five miRs were not differentially expressed in 21 5 cells. These eight miRs were not evaluated further. The expression profile of the remaining 16 miRs revealed that they were modulated by IFN b and or HCV. In particular, concordant modu