Based on the SEAP activities measured from multiple sampling, the protein expression levels of HCV genome-length and subgenomic replicons were comparable ( Figure S1A ). Core protein expression levels, on the other hand, suggested that Core-on cells produced higher levels of core protein than the genome-length replicon cells ( Figure S1B ). To identify the subcellular location of HCV proteins in genome-length replicon, subgenomic replicon, and Core-on cells, immunogold EM was carried out with antibodies against core, NS5A, and NS5B proteins. The majority of core, NS5A, and NS5B proteins were located in the mitochondria and the ER with minor differences in their distribution within these organelles ( Figure 1A and Table S1 ). Positive signals were also observed in the nucleus, lipid droplets, and the Golgi. NS5A signals were observed in autophagocytic vacuoles in 25% of the electron micrographs examined, with an average signal intensity of 3-6 gold particles per autophagocytic vacuole (Table S1 ).