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 concen trations of L-chicoric acid, HIV-1 was completely resistant to the com pound. Introduction of the mutant integrase containing a single glycin e-to-serine amino acid change at position 140 into the native, L-chico ric 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-chicori c acid inhibits integrase and that the drug is likely to interact at r esidues near the catalytic triad in the integrase active site.