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Antimicrobial Agents and Chemotherapy, July 2001, p. 2144-2146, Vol. 45, No. 7
0066-4804/01/$04.00+0   DOI: 10.1128/AAC.45.7.2144-2146.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Biochemical Mechanism of Human Immunodeficiency Virus Type 1 Reverse Transcriptase Resistance to Stavudine

Johan Lennerstrand,1,* David K. Stammers,2 and Brendan A. Larder1,*

Virco UK, Ltd, Cambridge CB4 0GA,1 and Structural Biology Division, The Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN,2 United Kingdom

Received 18 December 2000/Returned for modification 9 March 2001/Accepted 25 April 2001

We have found a close correlation between viral stavudine (d4T) resistance and resistance to d4T-triphosphate at the human immunodeficiency virus type 1 reverse transcriptase (RT) level. RT from site-directed mutants with 69S-XX codon insertions and/or conventional zidovudine resistance mutations seems to be involved in an ATP-dependent resistance mechanism analogous to pyrophosphorolysis, whereas the mechanism for RT with the Q151M or V75T mutation appears to be independent of added ATP for reducing binding to d4T-triphosphate.

* Corresponding author. Mailing address for Brendan A. Larder: Virco UK, Ltd, 184 Cambridge Sciences Rd., Milton Rd., Cambridge CB4 0GA, United Kingdom. Phone: 44 1 223 728 828. Fax: 44 1 223 728 801. E-mail: brendan.larder{at}vircolab.com. Mailing address for Johan Lennerstrand: Division of Clinical Virology, F68, Huddinge University Hospital, 141 86 Stockholm, Sweden. Phone: 46 8 58581304. Fax: 46 8 58581305. E-mail: johan.lennerstrand{at}impi.ki.se.

Antimicrobial Agents and Chemotherapy, July 2001, p. 2144-2146, Vol. 45, No. 7
0066-4804/01/$04.00+0   DOI: 10.1128/AAC.45.7.2144-2146.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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