Furin-mediated protein processing in infectious diseases and cancer

Braun, Elisabeth; Sauter, Daniel

Another nonenvelope protein that is cleaved by furin is the external core antigen (HBeAg) of hepatitis B virus (HBV). 82, 83 Cleaved HBeAg is secreted from infected cells and exerts immunosuppressive effects. 84 It has been suggested to act as a T-cell tolerogen that prevents killing of infected hepatocytes by cytotoxic T lymphocytes. 85 In contrast, uncleaved HBeAg may have the opposite effects as it is transported to the plasma membrane where it can trigger antiviral immune responses. 86 Thus, furin-mediated cleavage of HBeAg may affect the outcome of infection. Intriguingly, Han Chinese frequently harbour a single nucleotide polymorphism in the P1 promoter of the FUR gene that is associated with increased risk of developing persistent HBV infection with detectable amounts of HBeAg in the serum. 87 This polymorphism increases the binding efficiency of the hepatic transcription factor NF-E2, thereby most likely increasing furin expression. 87 Whether the observed increase in HBV persistence is the result of increased HBeAg processing and/or other effects of furin remains to be determined.