TABLE 1.

Genotypic and phenotypic characterization of recombinant HSV-1^a with regard to antivirals

Conserved region(s)	Nucleotide change(s)	Amino acid change(s)	Reference(s)d	IC50 (μg/ml) of ACV for:		SDf	Ratiog	IC50 (μg/ml) of FOS	SD	Ratio	IC50 (μg/ml) of CDV	SD	Ratio	IC50 (μg/ml) of ADV	SD	Ratio
				Mutant 1	Mutant 2
	wt	wt		0.0057	0.0064	±0.0012	1.00	15.0275	±1.61	1.00	0.1605	±0.0377	1.00	0.8475	±0.05	1.00
δ-C	A1654G	K552Eb	12, 44 (K513Ec)
δ-C	C1681T	P561S	12, 30, 46 (P522Sc)	0.0054	0.0054	±0.0007	0.85	13.6725	±1.91	0.91	0.2383	±0.0414	1.48	0.1800	±0.07	0.21
δ-C (exoIII)	G1717A	V573M	1	0.0122	0.0120	±0.0030	1.90	13.0340	±3.95	0.87	0.1861	±0.0530	1.16	1.1108	±0.42	1.31
δ-C (exoIII)	T1729C	Y577Hb	28, 29
II	G2099T	R700M	1	0.0044	0.0062	±0.0021	0.98	2.0350	±0.52	0.14	0.5886	±0.0385	3.67	0.4449	±0.01	0.52
II	G2143A	V715Mc	4, 5, 12, 46	0.0198	0.0182	±0.0045	2.86	12.1932	±2.76	0.81	0.0561	±0.0151	0.35	1.5076	±0.50	1.78
II	G2155A	A719T	6, 43 (A724Te)	0.0373	0.0377	±0.0043	5.94	32.6985	±2.57	2.18	0.2965	±0.0345	1.85	3.1958	±0.64	3.77
II	G2171A	S724N	1, 22, 34, 6, 43 (S729Ne)	0.0633	0.0627	±0.0253	9.87	40.4150	±2.96	2.69	0.3284	±0.0235	2.05	4.6750	±1.31	5.52
VI	C2332A	L778M	6, 43 (D783Me)	0.0300	0.0351	±0.0106	5.53	30.5800	±6.52	2.03	0.3281	±0.0561	2.04	2.7312	±1.70	3.22
VI	G2338A	D780N	6, 43 (D785Ne)	0.0445	0.0388	±0.0097	6.10	32.6100	±5.06	2.17	0.1937	±0.0387	1.21	2.3979	±0.31	2.83
VI	C2344A	L782I	4, 12, 46 (V781Ic)	0.0373	0.0408	±0.0086	6.43	34.3525	±4.60	2.29	0.2825	±0.0658	1.76	3.1875	±0.40	3.76
III	A2413C	K805Qc	12, 44	0.0032	0.0041	±0.0012	0.64	5.0978	±0.25	0.34	0.2914	±0.0660	1.82	0.2523	±0.06	0.30
III	C2462T	T821M	32	0.0294	0.0397	±0.0136	6.25	22.1939	±2.90	1.48	0.3392	±0.0364	2.11	2.3464	±0.53	2.77
III	C2536A	L846I	6, 43 (L850Ie)	0.0094	0.0096	±0.0013	1.52	10.5263	±2.26	0.70	0.2015	±0.0332	1.26	0.3913	±0.11	0.46
I	T2672G	F891C	26, 36	0.2222	0.2222	±0.0196	34.99	58.7450	±15.15	3.91	0.2795	±0.0542	1.74	5.9300	±0.08	7.00
I-VII	A2720T	D907V	6, 43 (D912Ve)	0.0280	0.0240	±0.0070	3.78	34.1425	±4.76	2.27	0.2555	±0.0594	1.59	2.1440	±0.68	2.53
I-VII	C2758T	P920S	6, 43	0.0051	0.0067	±0.0023	1.05	10.9750	±2.88	0.73	0.1037	±0.0130	0.65	0.8275	±0.09	0.98
VII	T2821C	Y941H	27	0.0555	0.0596	±0.0228	9.39	20.7158	±3.77	1.38	0.0629	±0.0164	0.39	4.8400	±1.31	5.71
V	C2883G	N961K	22	0.0369	0.0339	±0.008	5.34	12.4200	±2.12	0.83	0.2261	±0.1141	1.41	0.9250	±0.27	1.09
After V	C3019A	L1007M	1	0.0118	0.0117	±0.0012	1.84	8.8320	±1.20	0.59	0.1955	±0.0305	1.22	0.3050	±0.15	0.36
After V	T3083C	I1028T	1	0.0112	0.0111	±0.0023	1.74	8.6550	±2.15	0.58	0.3658	±0.0070	2.28	0.5373	±0.16	0.63
II and I-VII	G2171A and C2758T	S724N and P920S	6, 43	0.0811	0.0737	±0.0142	11.61	38.0000	±2.44	2.53	0.3819	±0.1218	2.38	6.5873	±1.59	7.77

^aTwo independently generated recombinant viruses were tested for each mutation. IC₅₀s are averages from at least two determinations for each of the recombinant viruses. Bold numbers indicate significant (i.e., at least twofold) changes in HSV drug susceptibility.

^bThis mutation could not be generated.

^cMutation originally described in the HCMV DNA pol (UL54) gene.

^dMutations shown in parentheses are those specifically described by the references.

^eMutation originally described in the HSV-2 DNA pol gene.

^fSD, standard deviation.

^gRatios of IC₅₀s for HSV recombinant mutants to that for parental wt recombinant.