Table 1. Mutations identified in JFH-1 full-length viruses^a that are less dependent on CyPA for infection.

CoFIM Sel.	Approach	Time	Mutations
			E2	NS5A
1	CyPA KD in JFH-1–infected cells	3 wk	I31T	D316Eb Y317N, D316E+Y317N
2	CyPA + CyPB KD in JFH-1–infected cells	3 wk	I31T	D316Eb Y317N, D316E+Y317Nc
3	Electroporation of JFH-1 RNA into CyPA KD cells	6 wk	T33A	Y317H, Y317R
4	Infection of CyPA KD cells with JFH-1	3 wk	I31T	Y317N
5	Infection of CyPA KD cells with JFH-1 harboring E2:I31T mutation	3 wk	I31Td	Y317N, Y317H

^aHCV sequences were obtained from intracellular viral RNA.

^bTwo types of nucleotide mutations (GAC → GAA; GAC → GAG) were found for the D316E mutation.

^cOut of 19 bacterial clones sequenced from this selection, 9 contained D316E, 7 contained Y317N, and 3 contained D316E + Y317N.

^dPreexisting E2 mutation.