ENV59-GP3 Immune Suppression via Inhibition of the Intermediate Conductance Calcium Activated Potassium Channel KCa3.1
Despite the extensive literature documenting a broad range of immune suppressive activity affecting different signal transduction pathways by retroviral derived immune suppressive peptides, no precise molecular mechanism of action (MoA) has been described. ENV59-GP3 is derived from an endogenous retroviral envelope protein and thus is expressed on the surface of immune cells. Therefore, it can be expected that it will interact with a surface receptor. We noted that KCa3.1 is a surface protein and that inhibition of KCa3.1 protected mice from developing severe colitis in two mouse models of inflammatory bowel disease [11], furthermore KCa3.1 inhibitor ameliorate the disease progression in EAE mice [19]. The overlap between the activity of KCa3.1 and our observations of the ENV59 activity made it a good candidate for further investigation.