simvastatin+interferon, why is there anincreased responce?

http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.1000598#pbio-1000598-g004
Host Defense against Viral Infection Involves Interferon Mediated Down-Regulation of Sterol Biosynthesis

quite complicated and studying various viruses, mainly dna viruses like hbv...the sum of it is for us: interferon+sim+vit d+alinia increase interferon response.this study explains why it happens on interferon+sim:

therapeutic Perspective

Several viruses including human CMV have been reported to be sensitive to statin administration [25],[26],[28]–[31]. Although the mechanism of action of most is not known, it has in some cases been correlated with a lower abundance of cholesterol in lipid rafts of cell membranes. A recognized potential complicating factor of using statins to specifically reduce cholesterol levels is that suppression of the proximal mevalonate arm also perturbs the synthesis of branch derivatives such as geranylgeraniol and farnesol involved in the protein farnesylation and prenylation pathways. In the case of HCV, the mechanisms of the inhibitory effects of the statins have been examined extensively and have been shown to relate to the prenylation of a host protein (FLB2) essential for viral replication [18],[57]. Recently a combination chemical screening study has been conducted to explore how the sterol and protein prenylation pathways work together to affect HCV in a replicon assay [32]. In agreement with those studies we also find reduced mCMV growth in siRNA knock-down experiments targeting enzymes in the isoprenod biosynthesis pathway. These studies indicate the importance of the geranylgeranylation to viral replication. Although, it is worth noting that the isoprenoid biosynthesis pathway is highly complicated with multiple branch points involving redundant enzymatic steps, sharing of subunits, and competing reactions. In our current study, we uncoupled the cholesterol synthesis pathway from non-steroidal modifications through targeted metabolic rescue and siRNA knock-down studies of mCMV and reveal an absolute requirement for the prenylation branch of the sterol pathway for mediating anti-viral effects. As further indicated from computational modeling work (unpublished data), targeting HMGCR is likely to have a broad range of non-specific effects on various efferent branch points of the pathway and thus may well not be ideal for anti-infective therapy. In addition, statins are also known to have a range of immune-modulatory activities by mechanisms yet to be fully characterized. In this context, it is worth noting that the activity of the type I interferons, especially IFNβ, have considerable overlap with many of the immune-related activities of statins [58]. Moreover, it is especially noteworthy that IFNβ treatment in patients has also been reported to have decreased plasma cholesterol levels [59],[60]. Since our studies uncover a molecular dependency of type 1 signaling, including a Tyk2 signaling component, this may provide an entirely new therapeutic pathway for lowering cholesterol. Moreover, our findings may have important implications for the development of broadly active new adjuvant strategies (e.g., the use of inhibitors of SREBP2 activity) to existing anti-infective therapies (e.g., antiviral drugs such as ganciclovir). On this basis we posit the principal of using metabolic modifiers, i.e. drugs that target metabolic pathways, of protective innate immunity as holding future promise for developing host-directed anti-viral therapies. Overall, this study supports the original concept [40],[41] of selectively targeting host pathways as an efficacious anti-infective strategy.

[Amlak]

I dont have enough knowledge about hep b but i would like to thank you stef2011 for sharing all you know about it with us. You are great sir.