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Journal of Virology, August 2001, p. 7202-7205, Vol. 75, No. 15
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.15.7202-7205.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Correlation between Viral Resistance to Zidovudine and Resistance at the Reverse Transcriptase Level for a Panel of Human Immunodeficiency Virus Type 1 Mutants

Johan Lennerstrand,1,* Kurt Hertogs,2 David K. Stammers,3 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, OX3 7BN Oxford,3 United Kingdom, and Virco N.V., B-2800 Mechelen, Belgium2

Received 14 September 2000/Accepted 28 April 2001

Using a large panel of human immunodeficiency virus type 1 site-directed mutants, we have observed a higher correlation than has previously been demonstrated between zidovudine (AZT)-triphosphate resistance data at the reverse transcriptase (RT) level and corresponding viral AZT resistance. This enhanced-resistance effect at the RT level was seen with ATP and to a lesser extent with PPi when ATP was added at physiological concentrations. The ATP-dependent mechanism (analogous to pyrophosphorolysis) appears to be dominant in the mutants bearing the D67N and K70R or 69 insertion mutations, whereas the Q151M mutation seems independent of ATP for decreased binding to AZT-triphosphate.

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

Journal of Virology, August 2001, p. 7202-7205, Vol. 75, No. 15
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.15.7202-7205.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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