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Journal of Virology, October 1998, p. 8420-8424, Vol. 72, No. 10
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

Peter J. King1 and W. Edward Robinson Jr.1,2,*

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.


* 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.


Journal of Virology, October 1998, p. 8420-8424, Vol. 72, No. 10
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.



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