Table 3.

Results of Antiviral Susceptibility and Replicative Capacity Assays of Novel HCMV Genetic Variants

GeneMutationNaPatient HistoryAntiviral Susceptibility (RI)b
GCVCDVFOSLMV
UL54G441S1CVID0.67 (±0.24)1 (±0.75)1.13 (±0.8)
UL54F460S1HSCT0.86 (±0.45)0.88 (±0.78)1.11 (±0.8)
UL54A543V2Kidney (2)1.5 (±0.1)10 (±5.37)1.21 (±0.27)
UL54R512C1Kidney110.74
UL54A928T1cCMV + 2 HSCT>3>3>3
UL56F345L1HSCT1.42 (±1.07)1.67 (±46)0.98 (±0.04)0.99 (±0.04)
UL56P800L1HSCT0.230.1311.11
GeneMutationNaPatient HistoryAntiviral Susceptibility (RI)b
GCVCDVFOSLMV
UL54G441S1CVID0.67 (±0.24)1 (±0.75)1.13 (±0.8)
UL54F460S1HSCT0.86 (±0.45)0.88 (±0.78)1.11 (±0.8)
UL54A543V2Kidney (2)1.5 (±0.1)10 (±5.37)1.21 (±0.27)
UL54R512C1Kidney110.74
UL54A928T1cCMV + 2 HSCT>3>3>3
UL56F345L1HSCT1.42 (±1.07)1.67 (±46)0.98 (±0.04)0.99 (±0.04)
UL56P800L1HSCT0.230.1311.11

Abbreviations: cCMV, congenital cytomegalovirus infection; CDV, cidofovir; CVID, common variable immunodeficiency; FOS, foscarnet; GCV, ganciclovir; HCMV, human cytomegalovirus; HSCT, hematopoietic stem cell transplant; LMV, letermovir; RI, resistance index.

NOTE: RI >3 is considered drug resistant and is indicated in bold.

a

Number of patients in whom the mutation was detected.

b

The RI is the half-maximal effective concentration ([EC50] µM) value for the mutant strain divided by the EC50 of the AD169 HCMV control strain. Each mutant was checked against different antiviral concentrations in triplicate. Each individual experiment was repeated 3 times for each mutant, except for R512C and P800L, which could only be performed once. Data are indicated as the mean of the 3 technical replicates.

Table 3.

Results of Antiviral Susceptibility and Replicative Capacity Assays of Novel HCMV Genetic Variants

GeneMutationNaPatient HistoryAntiviral Susceptibility (RI)b
GCVCDVFOSLMV
UL54G441S1CVID0.67 (±0.24)1 (±0.75)1.13 (±0.8)
UL54F460S1HSCT0.86 (±0.45)0.88 (±0.78)1.11 (±0.8)
UL54A543V2Kidney (2)1.5 (±0.1)10 (±5.37)1.21 (±0.27)
UL54R512C1Kidney110.74
UL54A928T1cCMV + 2 HSCT>3>3>3
UL56F345L1HSCT1.42 (±1.07)1.67 (±46)0.98 (±0.04)0.99 (±0.04)
UL56P800L1HSCT0.230.1311.11
GeneMutationNaPatient HistoryAntiviral Susceptibility (RI)b
GCVCDVFOSLMV
UL54G441S1CVID0.67 (±0.24)1 (±0.75)1.13 (±0.8)
UL54F460S1HSCT0.86 (±0.45)0.88 (±0.78)1.11 (±0.8)
UL54A543V2Kidney (2)1.5 (±0.1)10 (±5.37)1.21 (±0.27)
UL54R512C1Kidney110.74
UL54A928T1cCMV + 2 HSCT>3>3>3
UL56F345L1HSCT1.42 (±1.07)1.67 (±46)0.98 (±0.04)0.99 (±0.04)
UL56P800L1HSCT0.230.1311.11

Abbreviations: cCMV, congenital cytomegalovirus infection; CDV, cidofovir; CVID, common variable immunodeficiency; FOS, foscarnet; GCV, ganciclovir; HCMV, human cytomegalovirus; HSCT, hematopoietic stem cell transplant; LMV, letermovir; RI, resistance index.

NOTE: RI >3 is considered drug resistant and is indicated in bold.

a

Number of patients in whom the mutation was detected.

b

The RI is the half-maximal effective concentration ([EC50] µM) value for the mutant strain divided by the EC50 of the AD169 HCMV control strain. Each mutant was checked against different antiviral concentrations in triplicate. Each individual experiment was repeated 3 times for each mutant, except for R512C and P800L, which could only be performed once. Data are indicated as the mean of the 3 technical replicates.

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