TABLE 5.

Genotypic characterization of TK and DNA polymerase from 25 drug-resistant HSV clinical isolatesc

Isolate no.Patient ageClinical contextSampleHSV typePhenotypic susceptibility (EC50 [μM])TK mutationsDNA polymerase mutations
ACVFOSNatural polymorphismResistanceaUnknownbNatural polymorphismResistanceaUnknownb
121BMTMouth1>50<66C6G N23S K36E L42P G240E A265TNo mutationA207PS33G A330R N425T V905M
218BMTBlood111<66C6G N23S K36E R41H A192V A265TNo mutationL170PS33G A330R V905M T1208A
377ICEye135<66N23S K36E R89Q A265TNo mutationY53DS33G A330R V905M E1005K
451BMTAnal116<66N23S K36E−1C 553 = frameshiftS33G A330R A899VL1188F
58Wiskott-AldrichLip116<66N23S K36E A192V G251C A265T V267L P268T−1G 856 = frameshiftA330R V905M T1208AH98Y
637BMTSkin126<66N23S K36E R89Q+1G 437-438 = Stop 225S33G A330R A646T S1123L P1124H T1208AR1229I
759CLLGingiva131<66N23S K36E R89Q+1C 464-465 = Stop 228S33G A330R P1124H T1208AA870G
839BMTMouth110<66N23S K36E R89Q+1G 437-438 = Stop 228A330R P875S V905M P1124H T1208A
952BMTPalate1>50106N23S K36E R89Q+1G 437-438 = Stop 228S33G A330R V905M A1203T T1208A
108ALLBAL fluid122<66N23S K36E R89Q A265TC336YS33G A330R V905M
118BMTMouth1>50644N23S K36E G251C A265T P268TNo mutationR176WS33G A330R P1124H T1208AS724NV117L L267M
1247HIVGenital243<66G39E N78D L140FNo mutationS66P A72SA9T P15S L60P
1345HIVGenital233<66NoneNo mutationM183IA9T P15S R41H L60P E139K A232T
1443HIVGenital22492G39E N78DNo mutationM70RNoneA724V
1553HIVAnal21199NoneR221HA9T P15S L60P
1652HIVGenital2>50<66NoneD137StopA9T P15S L60P
1734HIVGenital2>50<66G39E N78DQ222StopA9T P15S L60P T801P
1837HIVAnal218<66A27T G39E N78D−1C 556 = Stop 263S29AA9T P15S L60P E678G del DD676-677
1955HIVAnal2>50<66G39E+2G 439-440 = Stop 184A9T P15S L60P del DGDE683-686
2063HIVAnal2>50<66G39E−1C 467 = Stop 183A9T P15S L60P E139K T801P
2139HIVLip2>5089G39E N78D L140F−1C 452 = Stop 183P15S L60P E678G
2244HIVGenital2>5076G39E N78D L140F+1G 439-440 = Stop 229A9T P15S L60P E678GY823C
2344BMTAnal2>50<66G39E N78D L140F+1G 439-440 = Stop 229A9T P15S L60PI291V
2470CLLAnal2>50<66G39E−1G 440 = Stop 229A9T P15S L60P E139KH837R
2539HIVGenital242145NoneNo mutationI101SNoneD785NV544A
  • a Previously described resistance mutations.

  • b Not previously described as known polymorphism or associated with resistance.

  • c BMT, bone marrow transplantation; IC, immunocompetent individual; ALL, acute lymphoblastic leukemia; CLL, chronic lymphocytic leukemia; BAL, bronchoalveolar lavage. The EC50 cutoff values for resistance to ACV and FOS were 7 and 330 μM, respectively.