Antiviral therapies targeting the BMP/SMAD/hepcidin signalling pathway

摘要

Methods of treatment and screening methods to identify therapeutic agents for viral infections (especially influenza A and hepatitis C virus) are disclosed wherein the signalling pathway (figure 1) from cellular iron detection via BMP6, Type I and II BMP receptors, SMAD1, SMAD4, SMAD5 and SMAD8 leads to enhanced expression of the HAMP gene encoding Hepcidin is modulated by agonists or antagonists, preferably of BMP6 or of the putative BMP receptor inhibitor TMPRSS6. The negative regulators SMAD6, SMAD7 and hemojuvelin are also implicated. The anti-influenza effects of BMP6 are shown in HuH7 hepatoma cells along with the altered iron-regulatory pathway in HCV infected hepatic cells.