TABLE 2.
Comparison of mutation rates in five genomic regions between untreated replicating HCV RNAsa and replicating RNAs treated with RBV or IFN
| Region and condition | No. of clones | No. (%) of mutant clones | Nonsynonymous/synonymous substitutions | Error generation rate (10−3) |
|---|---|---|---|---|
| 5′ UTR | ||||
| T7/H77 | 11 | 0 | 0 | 0 |
| + RBV (50 μM) | 15 | 3 (20) | 0/3 | 0.7 |
| + RBV (400 μM) | 14 | 3 (21) | 0/3 | 0.7 |
| + IFN (100,000 IU) | 13 | 0 | 0 | 0 |
| Core | ||||
| T7/H77 | 20 | 0 | 0 | 0 |
| + RBV (50 μM) | 14 | 7 (50) | 8/4 | 1.9b |
| + RBV (400 μM) | 20 | 4 (20) | 5/1 | 0.6c |
| + IFN (100,000 IU) | 11 | 4 (36) | 3/2 | 1.0d |
| E1/E2 | ||||
| T7/H77 | 11 | 4 (36) | 4/5 | 1.7e |
| + RBV (50 μM) | 20 | 12 (60) | 11/4 | 1.5f |
| + RBV (400 μM) | 20 | 7 (35) | 9/4 | 1.2 |
| + IFN (100,000 IU) | 12 | 10 (83) | 10/6 | 2.8g |
| NS5A | ||||
| T7/H77 | 14 | 0 | 0 | 0 |
| + RBV (50 μM) | 20 | 5 (20) | 12/0 | 2.5h |
| + RBV (400 μM) | 14 | 2 (14) | 3/0 | 0.9 |
| + IFN (100,000 IU) | 18 | 3 (16) | 5/1 | 1.4 |
| NS5B | ||||
| T7/H77 | 17 | 4 (17) | 4/1 | 0.7 |
| + RBV (50 μM) | 18 | 7 (39) | 9/4 | 1.7 |
| + RBV (400 μM) | 17 | 6 (35) | 5/2 | 1 |
| + IFN (100,000 IU) | 11 | 2 (18) | 2/1 | 0.7 |
a
T7/H77.
b
Four nucleotide insertions (2 stop codons). P < 0.00006 relative to untreated T7/H77.
c
P < 0.05 relative to untreated T7/H77.
d
P < 0.01 relative to untreated T7/H77.
e
P < 0.04 relative to untreated T7/H77.
f
One nucleotide insertion (one stop codon); one nucleotide deletion.
g
Four nucleotide insertions. P < 0.03 relative to untreated T7/H77.
h
P < 0.06 relative to untreated T7/H77.