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
Right arrow Citation Map
Services
Right arrow E-mail this article to a friend
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 Arts, E. J.
Right arrow Articles by Wainberg, M. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Arts, E. J.
Right arrow Articles by Wainberg, M. A.

 Previous Article  |  Next Article 

J Virol, June 1998, p. 4858-4865, Vol. 72, No. 6
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

3'-Azido-3'-Deoxythymidine (AZT) Mediates Cross-Resistance to Nucleoside Analogs in the Case of AZT-Resistant Human Immunodeficiency Virus Type 1 Variants

Eric J. Arts,1,* Miguel E. Quiñones-Mateu,1 Jamie L. Albright,1 James-Paul Marois,2 Charles Hough,2 Zhengxian Gu,2 and Mark A. Wainberg2

Division of Infectious Diseases, Department of Medicine, Case Western Reserve University, Cleveland, Ohio 44106,1 and McGill AIDS Centre, Lady Davis Institute-Jewish General Hospital, Montreal, Quebec, Canada H3T 1E22

Received 20 January 1998/Accepted 20 March 1998

Difficulties in deciphering the mechanisms of 3'-azido-3'-deoxythymidine (AZT)-resistance by human immunodeficiency virus type 1 (HIV-1) variants are due in part to an inability to reconstitute resistance in vitro using AZT-resistant reverse transcriptases. We decided to characterize mechanisms of AZT resistance in tissue culture infections by studying the ability of drug-resistant viruses to synthesize viral DNA in the presence or absence of drug. Through use of PCR amplifications, we discovered an AZT-mediated stimulation of reverse transcription by AZT-resistant viruses carrying the M41L and T215Y mutations that can apparently override the inhibitory effects of AZT-5'-triphosphate. In addition, the presence of AZT also causes viruses containing the M41L and T215Y substitutions to have diminished sensitivity to other nucleoside analogs (i.e., ddC, ddI, and d4T). This AZT-mediated cross-resistance may help to explain the virological failure of treatment regimens that included ddI plus AZT or ddC plus AZT in situations in which the T215Y and/or M41L mutations were present (F. Brun-Vézinet, C. Boucher, C. Loveday, D. Descamps, V. Fauveau, J. Izopet, D. Jeffries, S. Kaye, C. Krzyanowski, A. Nunn, R. Schuurman, J. M. Seigneurin, C. Tamalet, R. Tedder, J. Weber, and G. J. Weverling, Lancet 350:983-990, 1997). Our results suggest that the use of AZT may be contraindicated in those patients for whom resistance to this compound (M41L and/or T215Y) has been demonstrated.

* Corresponding author. Mailing address: Division of Infectious Diseases, BRB 1029, Case Western Reserve University, 10900 Euclid Ave., Cleveland, OH 44106. Phone: (216) 368-8904. Fax: (216) 368-2034. E-mail: eja3{at}po.cwru.edu.

J Virol, June 1998, p. 4858-4865, Vol. 72, No. 6
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Coburn, G. A., Cullen, B. R. (2002). Potent and Specific Inhibition of Human Immunodeficiency Virus Type 1 Replication by RNA Interference. J. Virol. 76: 9225-9231 [Abstract] [Full Text]  
  • Shafer, R. W. (2002). Genotypic Testing for Human Immunodeficiency Virus Type 1 Drug Resistance. Clin. Microbiol. Rev. 15: 247-277 [Abstract] [Full Text]  
  • Imamichi, T., Berg, S. C., Imamichi, H., Lopez, J. C., Metcalf, J. A., Falloon, J., Lane, H. C. (2000). Relative Replication Fitness of a High-Level 3'-Azido-3'-Deoxythymidine-Resistant Variant of Human Immunodeficiency Virus Type 1 Possessing an Amino Acid Deletion at Codon 67 and a Novel Substitution (Thrright-arrowGly) at Codon 69. J. Virol. 74: 10958-10964 [Abstract] [Full Text]  
  • Stoddart, C. A., Moreno, M. E., Linquist-Stepps, V. D., Bare, C., Bogan, M. R., Gobbi, A., Buckheit, R. W. Jr., Bedard, J., Rando, R. F., McCune, J. M. (2000). Antiviral Activity of 2'-Deoxy-3'-Oxa-4'-Thiocytidine (BCH-10652) against Lamivudine-Resistant Human Immunodeficiency Virus Type 1 in SCID-hu Thy/Liv Mice. Antimicrob. Agents Chemother. 44: 783-786 [Abstract] [Full Text]  
  • Wisniewski, M., Palaniappan, C., Fu, Z., Le Grice, S. F. J., Fay, P., Bambara, R. A. (1999). Mutations in the Primer Grip Region of HIV Reverse Transcriptase Can Increase Replication Fidelity. J. Biol. Chem. 274: 28175-28184 [Abstract] [Full Text]  


Copyright © 2010 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»