Amino acid deletion at codon 67 and Thr-to-Gly change at codon 69 of human immunodeficiency virus type 1 reverse transcriptase confer novel drug resistance profiles.
The potential roles of an amino acid deletion at codon 67 (Delta67) and a Thr-to-Gly change at codon 69 (T69G) in the reverse transcriptase of human immunodeficiency virus (HIV) type 1 in drug sensitivity and relative replication fitness were studied. Our results suggest that the Delta67 and T69G changes can be categorized as mutations associated with multidrug resistance. The combination of both mutations with an L74I change (Delta67+T69G/L74I) leads to a novel 3'-azido-3'-deoxythymidine resistance motif and compensates for impaired HIV replication.
Laboratory of Molecular Retrovirology, Clinical Services Program, Science Applications International Corporation-Frederick, National Cancer Institute-Frederick, Frederick, Maryland 21702-1201, USA. timamichi@nih.gov
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D020816:Amino Acid Motifs; D019943:Amino Acid Substitution / Q000235:genetics*; D019380:Anti-HIV Agents / Q000494:pharmacology; D003062:Codon / Q000235:genetics*; D004352:Drug Resistance, Microbial / Q000235:genetics*; D018432:Drug Resistance, Multiple / Q000235:genetics; D014644:Genetic Variation / Q000235:genetics; D005998:Glycine / Q000235:genetics / Q000378:metabolism; D054303:HIV Reverse Transcriptase / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D015497:HIV-1 / Q000187:drug effects / Q000201:enzymology* / Q000235:genetics / Q000502:physiology; D006801:Humans; D020128:Inhibitory Concentration 50; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology; D017384:Sequence Deletion / Q000235:genetics*; D013912:Threonine / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014779:Virus Replication / Q000187:drug effects
D019380:Anti-HIV Agents; D003062:Codon; D018894:Reverse Transcriptase Inhibitors; D013912:Threonine; D054303:HIV Reverse Transcriptase; D005998:Glycine