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Journal of Virology, October 1998, p. 8420-8424, Vol. 72, No. 10
Departments of Microbiology and Molecular
Genetics1 and
Pathology,2 University of
California, Irvine, California 92697
Received 7 April 1998/Accepted 24 June 1998
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.
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
Resistance to the Anti-Human Immunodeficiency
Virus Type 1 Compound L-Chicoric Acid Results from a
Single Mutation at Amino Acid 140 of Integrase
*
Corresponding author. Mailing address: Department of
Pathology, D440 Med Sci I, University of California, Irvine, CA
92697-4800. Phone: (949) 824-3431. Fax: (949) 824-2505. E-mail:
ewrobins{at}uci.edu.
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