TABLE 1.

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

Conserved region(s)Nucleotide change(s)Amino acid change(s)Reference(s)dIC50 (μg/ml) of ACV for:SDfRatiogIC50 (μg/ml) of FOSSDRatioIC50 (μg/ml) of CDVSDRatioIC50 (μg/ml) of ADVSDRatio
Mutant 1Mutant 2
wtwt0.00570.0064±0.00121.0015.0275±1.611.000.1605±0.03771.000.8475±0.051.00
δ-CA1654GK552Eb12, 44 (K513Ec)
δ-CC1681TP561S12, 30, 46 (P522Sc)0.00540.0054±0.00070.8513.6725±1.910.910.2383±0.04141.480.1800±0.070.21
δ-C (exoIII)G1717AV573M10.01220.0120±0.00301.9013.0340±3.950.870.1861±0.05301.161.1108±0.421.31
δ-C (exoIII)T1729CY577Hb28, 29
IIG2099TR700M10.00440.0062±0.00210.982.0350±0.520.140.5886±0.03853.670.4449±0.010.52
IIG2143AV715Mc4, 5, 12, 460.01980.0182±0.00452.8612.1932±2.760.810.0561±0.01510.351.5076±0.501.78
IIG2155AA719T6, 43 (A724Te)0.03730.0377±0.00435.9432.6985±2.572.180.2965±0.03451.853.1958±0.643.77
IIG2171AS724N1, 22, 34, 6, 43 (S729Ne)0.06330.0627±0.02539.8740.4150±2.962.690.3284±0.02352.054.6750±1.315.52
VIC2332AL778M6, 43 (D783Me)0.03000.0351±0.01065.5330.5800±6.522.030.3281±0.05612.042.7312±1.703.22
VIG2338AD780N6, 43 (D785Ne)0.04450.0388±0.00976.1032.6100±5.062.170.1937±0.03871.212.3979±0.312.83
VIC2344AL782I4, 12, 46 (V781Ic)0.03730.0408±0.00866.4334.3525±4.602.290.2825±0.06581.763.1875±0.403.76
IIIA2413CK805Qc12, 440.00320.0041±0.00120.645.0978±0.250.340.2914±0.06601.820.2523±0.060.30
IIIC2462TT821M320.02940.0397±0.01366.2522.1939±2.901.480.3392±0.03642.112.3464±0.532.77
IIIC2536AL846I6, 43 (L850Ie)0.00940.0096±0.00131.5210.5263±2.260.700.2015±0.03321.260.3913±0.110.46
IT2672GF891C26, 360.22220.2222±0.019634.9958.7450±15.153.910.2795±0.05421.745.9300±0.087.00
I-VIIA2720TD907V6, 43 (D912Ve)0.02800.0240±0.00703.7834.1425±4.762.270.2555±0.05941.592.1440±0.682.53
I-VIIC2758TP920S6, 430.00510.0067±0.00231.0510.9750±2.880.730.1037±0.01300.650.8275±0.090.98
VIIT2821CY941H270.05550.0596±0.02289.3920.7158±3.771.380.0629±0.01640.394.8400±1.315.71
VC2883GN961K220.03690.0339±0.0085.3412.4200±2.120.830.2261±0.11411.410.9250±0.271.09
After VC3019AL1007M10.01180.0117±0.00121.848.8320±1.200.590.1955±0.03051.220.3050±0.150.36
After VT3083CI1028T10.01120.0111±0.00231.748.6550±2.150.580.3658±0.00702.280.5373±0.160.63
II and I-VIIG2171A and C2758TS724N and P920S6, 430.08110.0737±0.014211.6138.0000±2.442.530.3819±0.12182.386.5873±1.597.77
  • a Two 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.

  • b This mutation could not be generated.

  • c Mutation originally described in the HCMV DNA pol (UL54) gene.

  • d Mutations shown in parentheses are those specifically described by the references.

  • e Mutation originally described in the HSV-2 DNA pol gene.

  • f SD, standard deviation.

  • g Ratios of IC50s for HSV recombinant mutants to that for parental wt recombinant.