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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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