Positional effect of mutations in 5'UTR of hepatitis C virus 4a on patients' response to therapy

Table 1 Distribution of mutations in different loops of domain III in SVR compared with BT patients

Mutation	Position	Region	No. of patients			Effect on ΔG (kcal/mol)
			SVR (n = 14)	BT-PreT (n = 5)	BT Post-T (n = 5)
C-T	148	Junction joining stem-loop IIIa b, c & d	-	-	1	Increased
G-T	158	Loop IIIa	-	1	4	Increased
T-A	175	Loop IIIb	1	-	-	No effect
G & A ins	179		2	-	-	Increased
T ins.	180		1	-	-	Increased
T ins.	181		1	-	-	Increased
C-T	186		-	-	1	No effect
TTT-GGG	194-196		-	1	-	No effect
C ins.	205		1	-	-	No effect
T-C	199		-	-	1	No effect
G-A	243	Junction joining stem-loop IIIa, b, c & d	5	1	4	No effect
C-T	254	Loop IIId	-	1	1	Decreased
A-C	260		1	-	1	Decreased
A-T	260		1	-	-	Decreased
G-T	261		1	-	-	Increased
G-T	268		-	1	1	Decreased
T-C	269		-	1	1	Decreased
G ins.	270		-	1	1	Decreased
A-C	275		2	-	-	Decreased

The distribution of the observed mutations in different loops of domain III in sustained viral response (SVR) and breakthrough (BT) patients is shown. The majority of mutations (14/19) were simple substitutions whereas 5/19 were insertions. Most mutations were found in stem-loops IIIb and d. The effect of each mutation on the overall thermodynamic stability of the related domain is indicated. Decreased ΔG means increased stability and vice versa. Pre-T: Pre-treatment; Post-T: Post-treatment.

Table 2 Distribution of the 19 identified mutations in different loops of domain III in SVR and BT patients

Region	Responder (SVR; %)	BT pre treatment (%)	BT post treatment (%)
Stem-loop IIIa (156-171)	-	14.3	10
Stem-loop IIIb (172-227)	50	14.3	20
Stem-loop IIIc (228-238)	-	-	-
Stem-loop IIId (253-279)	40	57.1	50
Junction joining stem-loop IIIa, b, c, & d (141-153) & (239-252)	10	14.3	20

Ten mutations, out of the 19 identified point mutations, are found in responders (SVR). Five of these mutations are found in loop IIIb, four in IIId, and one in the junction. Seven mutations are found in the BT pre-treatment group (four in loop IIId and one in each of loop IIIa, IIIb, and junction). Ten mutations were detected in BT post-treatment (five in IIId, 2 in each of IIIb and the junction, and one in loop IIIa).