Sensitivity of (138 Glu-->Lys) mutated human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) to HIV-1-specific RT inhibitors.
Human immunodeficiency virus type 1 (HIV-1) recombinant reverse transcriptase (RT) containing lysine (Lys) instead of glutamic acid (Glu) at position 138 proved fully resistant to the inhibitory effect of TSAO derivatives, but retained marked sensitivity to all other HIV-1-specific inhibitors investigated. In contrast, 181 Tyr-->Cys mutated RT lost sensitivity to all HIV-1-specific inhibitors. There was a close correlation between the sensitivity/resistance pattern of HIV-1-specific inhibitors against mutated (138 Glu-->Lys) recombinant HIV-1 RT and mutant virus strains selected for resistance against TSAO-m3T in cell culture and proven to contain the 138-Lys mutation as the sole mutation within the amino acid 50-270 region of their RT.
Balzarini
J
J
Rega Institute for Medical Research, Katholieke Universiteit Leuven, Belgium.
Kleim
J P
JP
Riess
G
G
Camarasa
M J
MJ
De Clercq
E
E
Karlsson
A
A
D000998:Antiviral Agents; D004352:Drug Resistance, Microbial; D005971:Glutamates / Q000737:chemistry; D054303:HIV Reverse Transcriptase; D015497:HIV-1 / Q000187:drug effects* / Q000201:enzymology; D006801:Humans; D016297:Mutagenesis, Site-Directed; D011728:Pyridones / Q000494:pharmacology; D012194:RNA-Directed DNA Polymerase / Q000737:chemistry; D011994:Recombinant Proteins; D018894:Reverse Transcriptase Inhibitors; D013141:Spiro Compounds; D013329:Structure-Activity Relationship; D013936:Thymidine / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology; D014529:Uridine / Q000031:analogs & derivatives
D000998:Antiviral Agents; D005971:Glutamates; D011728:Pyridones; D011994:Recombinant Proteins; D018894:Reverse Transcriptase Inhibitors; D013141:Spiro Compounds; D054303:HIV Reverse Transcriptase; D012194:RNA-Directed DNA Polymerase; D013936:Thymidine; C075132:TSAO-T; D014529:Uridine