Hepatitis B virus core protein interacts with CD59 to promote complement-mediated liver inflammation during chronic hepatitis B virus infection

The inflammatory response mediated by the immune system is the major cause of hepatitis B virus (HBV)-associated liver injury. Here, we identified CD59, as a novel HBc-interacting protein in hepatocytes by tandem affinity purification (TAP) screening. The expression of CD59 was markedly down-regulated in HBc-transfected HepG2 or HepG2.215 cells, which resulted in an upshift of hepatocyte sensitivity to membrane attack complex (MAC)-induced cell lysis. These results were consistent with the accumulation of MACs in the liver of HBV-infected patients. Additional analyses using laser confocal microscopy, quantitative PCR and flow cytometry revealed that CD59 was specifically translocated to the nucleus upon binding to HBc, which induced the down-regulation of CD59 on both the mRNA and protein levels.