Integration of an HCV-derived oncogenic signal with an HCV-independent one. Individually, signals are subliminal and nononcogenic (green arrows); on integration, signals may become supraliminal and oncogenic (red arrows). Four examples of signal integration are shown. (A) HCV-E2 protein-CD81 interaction and specific antigen-surface Ig interaction. (B) An endogenous defect (eg irf-1^−/− mice) and HCV infecting a B cell. (C) HCV and EBV coinfection. (D) HCV infection and signal X (eg, environmental factor or others).