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Antimicrobial Agents and Chemotherapy, August 1999, p. 2077-2080, Vol. 43, No. 8
0066-4804/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

A New Point Mutation (P157S) in the Reverse Transcriptase of Human Immunodeficiency Virus Type 1 Confers Low-Level Resistance to (-)-beta -2',3'-Dideoxy-3'-Thiacytidine

Robert A. Smith,1 George J. Klarmann,1 Kirsten M. Stray,1 Uta K. von Schwedler,1 Raymond F. Schinazi,2,3 Bradley D. Preston,1,* and Thomas W. North4

Eccles Institute of Human Genetics, University of Utah, Salt Lake City, Utah 841121; Georgia VA Research Center for AIDS and HIV Infections2 and Department of Pediatrics, Emory University School of Medicine,3 Decatur, Georgia 30033; and Center for Comparative Medicine, University of California, Davis, California 956164

Received 18 November 1998/Returned for modification 8 March 1999/Accepted 13 May 1999

A P157S mutation in the reverse transcriptase (RT) of human immunodeficiency virus type 1 conferred fivefold resistance to (-)-beta -2',3'-dideoxy-3'-thiacytidine in cell culture. Interestingly, the P157S mutation resulted in increased sensitivity (two- to threefold) to 3'-azido-3'-deoxythymidine (AZT) and to (R)-9-(2-phosphonylmethoxypropyl)adenine (PMPA). A similar increase in susceptibility to AZT and to PMPA was also conferred by the M184V mutation in RT.

* Corresponding author. Mailing address: Eccles Institute of Human Genetics, University of Utah, Salt Lake City, UT 84112. Phone: (801) 585-6342. Fax: (801) 585-3501. E-mail: bpreston{at}hci.utah.edu.

Antimicrobial Agents and Chemotherapy, August 1999, p. 2077-2080, Vol. 43, No. 8
0066-4804/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Smith, R. A., Anderson, D. J., Preston, B. D. (2006). Hypersusceptibility to Substrate Analogs Conferred by Mutations in Human Immunodeficiency Virus Type 1 Reverse Transcriptase. J. Virol. 80: 7169-7178 [Abstract] [Full Text]  
  • Smith, R. A., Anderson, D. J., Preston, B. D. (2004). Purifying Selection Masks the Mutational Flexibility of HIV-1 Reverse Transcriptase. J. Biol. Chem. 279: 26726-26734 [Abstract] [Full Text]  
  • Diallo, K., Oliveira, M., Moisi, D., Brenner, B., Wainberg, M. A., Gotte, M. (2002). Pressure of Zidovudine Accelerates the Reversion of Lamivudine Resistance-Conferring M184V Mutation in the Reverse Transcriptase of Human Immunodeficiency Virus Type 1. Antimicrob. Agents Chemother. 46: 2254-2256 [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]  
  • Klarmann, G. J., Smith, R. A., Schinazi, R. F., North, T. W., Preston, B. D. (2000). Site-specific Incorporation of Nucleoside Analogs by HIV-1 Reverse Transcriptase and the Template Grip Mutant P157S. TEMPLATE INTERACTIONS INFLUENCE SUBSTRATE RECOGNITION AT THE POLYMERASE ACTIVE SITE. J. Biol. Chem. 275: 359-366 [Abstract] [Full Text]  


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