Table 1

Sequence analysis of coding changes in J6/JFH1 and derived viruses from mouse samples and in vitro passages of mouse samples.

HCV gene	Core	Core	E2	E2	E2	NS2	NS2	NS2	NS2	NS2	NS2	NS3	NS5A	NS5A	NS5A	NS5B
Nucleotide number and type
J6/JFH1 position	572	621	1641	1679	2528	2952	2955	2964	2965	2978	3051	4306	7069	7164	7389	7697
H77 abs. ref. (AF009606)	573	622	1642	1680	2517	2941	2944	2953	2954	2967	3040	4295	7070	7165	7390	7632
Nucleotide of J6/JFH1	A	C	A	T	T	G	G	A	T	G	A	C	G	T	A	A
J6/JFH1 Infected human liver chimeric mouse samples
B139—serum (ex vivo)	•	T/C	•	•	•	•	•	A/g	A/t	•	•	•	•	T/A	•	•
B139—1st passage in cell culture	•	T/c	•	•	•	•	•	•	A	•	•	•	•	A/t	•	•
B156—serum (ex vivo)	•	T/C	•	•	•	•	•	A/g	A/t	•	•	•	•	T/a	•	•
B156—1st passage in cell culture	•	T/c	•	•	•	•	•	•	A	•	•	•	•	A	•	•
J6/JFH1_ΔHVR1 Infected human liver chimeric mouse samples
K826R—plasma (ex vivo)	•	•	•	•	G/t	T	•	•	•	•	•	•	•	•	•	•
K826R—1st passage in cell culture	•	•	•	•	G	T	•	•	•	•	•	•	•	•	•	•
K890R—plasma (ex vivo)	•	•	G/a	G	•	•	A	•	•	•	G	•	•	•	G/A	G/A
K890R—1st passage in cell culture	•	•	G	G	•	•	A	•	•	•	G	•	•	•	•	•
B150R—plasma (ex vivo)	A/c	•	•	•	•	•	•	A/g	•	C/g	•	•	•	•	•	•
B150R—1st passage in cell culture	C/A	•	•	•	•	•	•	•	•	C/g	•	•	•	•	•	•
J6/JFH1_A876P Infected human liver chimeric mouse samples
K1219RL—1st passage in cell culture	•	•	•	•	•	•	•	•	•	C	•	•	•	•	•	•
K1216L—1st passage in cell culture	•	•	•	•	•	•	•	•	•	C	•	•	C/G	•	•	•
K1207—1st passage in cell culture	•	•	•	•	•	•	•	•	•	C	•	G/c	•	•	•	•
J6/JFH1_ΔHVR1/A876P Infected human liver chimeric mouse samples
B413L—1st passage in cell culture	A/g	•	•	•	•	•	•	•	•	C	•	•	•	•	•	•
B413RL—1st passage in cell culture	•	•	•	•	G	•	•	•	•	C	•	•	•	•	•	•
K1207R—1st passage in cell culture	A/g	•	•	T/g	T/g	•	•	•	•	C	•	•	•	•	•	•
K1207L—1st passage in cell culture	•	•	•	•	G/t	•	•	•	•	C	•	•	•	•	•	•
Amino acid number and type
J6/JFH1 position	78	94	434	447	730	871	872	875	875	880	904	1322	2243	2275	2350	2453
H77 abs. ref. (AF009606)	78	94	434	447*	726*	867	868	871	871	876	900	1318	2243	2275	2350	2431
Change relative to J6/JFH1	K→Q/E	A→V	H→R	F→V	L→V	R→L	G→D	D→G	D→E	A→P	Y→C	C→W	Q→H	M→K	K→R	I→V

The entire open reading frame of viruses was sequenced. The cell culture viruses were sequenced at peak of infection. Only nucleotide changes resulting in amino acid changes are shown. Capital letters indicate the presence of one determinate sequence peak. Two capital letters separated by a slash indicate the presence of a 50/50 quasispecies, whereas a capital letter separated by a slash from a lowercase letter indicates a quasispecies with a dominant versus a minor sequence. Light grey indicates mutation cluster between amino acid positions 867–876. Dark grey indicates mutation introduced to the virus genome by cloning.
*Mutations F447V and L726V were generated for J6/JFH1 and J6/JFH1_ΔHVR1 recombinant viruses and were found to have minor in vitro adaptive fitness effects for the hypervariable region 1 (HVR1)-deleted variant, but not for J6/JFH1, and to have no effect on neutralisation susceptibility of J6/JFH1_ΔHVR1 against H06 IgG.