This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by King, P. J.
Right arrow Articles by Robinson, W. E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by King, P. J.
Right arrow Articles by Robinson, W. E., Jr.

 Previous Article  |  Next Article 

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.


This article has been cited by other articles:

  • Kessl, J. J., Eidahl, J. O., Shkriabai, N., Zhao, Z., McKee, C. J., Hess, S., Burke, T. R. Jr, Kvaratskhelia, M. (2009). An Allosteric Mechanism for Inhibiting HIV-1 Integrase with a Small Molecule. Mol. Pharmacol. 76: 824-832 [Abstract] [Full Text]  
  • Jones, G. S., Yu, F., Zeynalzadegan, A., Hesselgesser, J., Chen, X., Chen, J., Jin, H., Kim, C. U., Wright, M., Geleziunas, R., Tsiang, M. (2009). Preclinical Evaluation of GS-9160, a Novel Inhibitor of Human Immunodeficiency Virus Type 1 Integrase. Antimicrob. Agents Chemother. 53: 1194-1203 [Abstract] [Full Text]  
  • Malet, I., Delelis, O., Valantin, M.-A., Montes, B., Soulie, C., Wirden, M., Tchertanov, L., Peytavin, G., Reynes, J., Mouscadet, J.-F., Katlama, C., Calvez, V., Marcelin, A.-G. (2008). Mutations Associated with Failure of Raltegravir Treatment Affect Integrase Sensitivity to the Inhibitor In Vitro. Antimicrob. Agents Chemother. 52: 1351-1358 [Abstract] [Full Text]  
  • Johnson, A. A., Marchand, C., Patil, S. S., Costi, R., Di Santo, R., Burke, T. R. Jr., Pommier, Y. (2007). Probing HIV-1 Integrase Inhibitor Binding Sites with Position-Specific Integrase-DNA Cross-Linking Assays. Mol. Pharmacol. 71: 893-901 [Abstract] [Full Text]  
  • Johnson, A. A., Sayer, J. M., Yagi, H., Patil, S. S., Debart, F., Maier, M. A., Corey, D. R., Vasseur, J.-J., Burke, T. R. Jr., Marquez, V. E., Jerina, D. M., Pommier, Y. (2006). Effect of DNA Modifications on DNA Processing by HIV-1 Integrase and Inhibitor Binding: ROLE OF DNA BACKBONE FLEXIBILITY AND AN OPEN CATALYTIC SITE. J. Biol. Chem. 281: 32428-32438 [Abstract] [Full Text]  
  • Lee, D. J., Robinson, W. E. Jr. (2006). Preliminary Mapping of a Putative Inhibitor-Binding Pocket for Human Immunodeficiency Virus Type 1 Integrase Inhibitors. Antimicrob. Agents Chemother. 50: 134-142 [Abstract] [Full Text]  
  • Lee, D. J., Robinson, W. E. Jr. (2004). Human Immunodeficiency Virus Type 1 (HIV-1) Integrase: Resistance to Diketo Acid Integrase Inhibitors Impairs HIV-1 Replication and Integration and Confers Cross-Resistance to L-Chicoric Acid. J. Virol. 78: 5835-5847 [Abstract] [Full Text]  
  • Shkriabai, N., Patil, S. S., Hess, S., Budihas, S. R., Craigie, R., Burke, T. R. Jr., Le Grice, S. F. J., Kvaratskhelia, M. (2004). Identification of an inhibitor-binding site to HIV-1 integrase with affinity acetylation and mass spectrometry. Proc. Natl. Acad. Sci. USA 101: 6894-6899 [Abstract] [Full Text]  
  • Kuznetsov, Y. G., Victoria, J. G., Robinson, W. E. Jr., McPherson, A. (2003). Atomic Force Microscopy Investigation of Human Immunodeficiency Virus (HIV) and HIV-Infected Lymphocytes. J. Virol. 77: 11896-11909 [Abstract] [Full Text]  
  • Fikkert, V., Van Maele, B., Vercammen, J., Hantson, A., Van Remoortel, B., Michiels, M., Gurnari, C., Pannecouque, C., De Maeyer, M., Engelborghs, Y., De Clercq, E., Debyser, Z., Witvrouw, M. (2003). Development of Resistance against Diketo Derivatives of Human Immunodeficiency Virus Type 1 by Progressive Accumulation of Integrase Mutations. J. Virol. 77: 11459-11470 [Abstract] [Full Text]  
  • Reinke, R., Lee, D. J., Robinson, W. E. Jr. (2002). Inhibition of Human Immunodeficiency Virus Type 1 Isolates by the Integrase Inhibitor L-731,988, a Diketo Acid. Antimicrob. Agents Chemother. 46: 3301-3303 [Abstract] [Full Text]  
  • Gray, D. E., Roberts, C. A., Rottinghaus, G. E., Garrett, H. E., Pallardy, S. G. (2001). Quantification of Root Chicoric Acid in Purple Coneflower by Near Infrared Reflectance Spectroscopy. Crop Sci. 41: 1159-1161 [Abstract] [Full Text]  
  • Pluymers, W., Neamati, N., Pannecouque, C., Fikkert, V., Marchand, C., Burke, T. R. Jr., Pommier, Y., Schols, D., De Clercq, E., Debyser, Z., Witvrouw, M. (2000). Viral Entry as the Primary Target for the Anti-HIV Activity of Chicoric Acid and Its Tetra-Acetyl Esters. Mol. Pharmacol. 58: 641-648 [Abstract] [Full Text]  
  • Zhu, K., Cordeiro, M. L., Atienza, J., Robinson, W. E. Jr., Chow, S. A. (1999). Irreversible Inhibition of Human Immunodeficiency Virus Type 1 Integrase by Dicaffeoylquinic Acids. J. Virol. 73: 3309-3316 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»