ENF susceptibilities of NL4-3/D36G mutants and clinical isolates carrying double substitutions in gp41 amino acid residues 36 to 45

Substitution(s)Data for NL4-3/D36G mutantsaData for primary clinical isolatesb
ENF IC50 (μg/ml)Fold change compared to NL4-3/D36G (parental virus)Baseline ENF IC50 (μg/ml)Treatment ENF IC50 (μg/ml)Fold change compared to baseline virus
NL4-3/D36G (parental virus)0.012
G36S + L44M0.181150.0063.791632
N42T + N43K0.388320.0071.762252
N42T + N43S0.727610.0062.031f339
V38A + N42D1.6851400.0221.074d49
V38A + N42T1.782149e
V38E + N42S6.156513e
N42T + L45Mc0.162140.1685.04230
Q40H + L45M0.805670.03310.776327
  • a Produced by site-directed mutagenesis of NL4-3, altered to match the consensus sequence at amino acid position 36 (aspartic acid replaced by glycine).

  • b On-treatment clinical isolates that carried double amino acid substitutions between amino acids 36 and 45 of gp41 and their paired baseline isolates that exhibited the consensus sequence, except as noted in footnote c.

  • c The L44M mutation was observed in the baseline isolate cultured in vitro. The sequence derived from plasma RNA had the consensus wild-type Leu at gp41 position 44. This patient developed N42T and L45M mutations upon treatment, but the L44M mutation was no longer present.

  • d The cultured on-treatment isolate contains a mixture of the consensus and the mutant amino acids at positions 38 and 42.

  • e Cultured isolates containing these mutations were not obtained from patients.

  • f The isolate also contained an S138A substitution in HR-2 of gp41 as a change from baseline.