Resistance to the anti-human immunodeficiency virus type 1 compound L-chicoric acid results from a single mutation at amino acid 140 of integrase.
L-Chicoric acid is an inhibitor of human immunodeficiency virus type 1 (HIV-1) integrase in vitro and of HIV-1 replication in tissue culture. Following 3 months of selection in the presence of increasing concentrations of L-chicoric acid, HIV-1 was completely resistant to the compound. Introduction of the mutant integrase containing a single glycine-to-serine amino acid change at position 140 into the native, L-chicoric acid-sensitive virus demonstrated that this change was sufficient to confer resistance to L-chicoric acid. These results confirm through natural selection previous biochemical studies showing that L-chicoric acid inhibits integrase and that the drug is likely to interact at residues near the catalytic triad in the integrase active site.
King
P J
PJ
Departments of Microbiology and Molecular Genetics, University of California, Irvine, California 92697, USA.
Robinson
W E
WE
D019943:Amino Acid Substitution; D019380:Anti-HIV Agents / Q000494:pharmacology*; D001483:Base Sequence; D002109:Caffeic Acids; D017931:DNA Primers; D004352:Drug Resistance, Microbial / Q000235:genetics*; D019427:HIV Integrase / Q000235:genetics*; D019428:HIV Integrase Inhibitors / Q000494:pharmacology*; D015497:HIV-1 / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D013386:Succinates / Q000494:pharmacology*
D019380:Anti-HIV Agents; D002109:Caffeic Acids; D017931:DNA Primers; D019428:HIV Integrase Inhibitors; D013386:Succinates; D019427:HIV Integrase; C100435:chicoric acid