FIG 8.

A proposed mechanism of the HCV NS5A-induced lysosomal degradation of HNF-1α via CMA. HCV NS5A interacts with HSC70 and recruits HSC70 to HNF-1α protein through an interaction between NS5A and HNF-1α. HSC70 interacts with HNF-1α at its CMA-targeting motif. Protein complexes are delivered to the lysosome by HSC70. HSC70 is recognized by LAMP2A, a lysosomal membrane protein. HNF-1α protein gets unfolded and translocated into the lysosome. HNF-1α is degraded in the lysosome by lysosomal proteases.