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

Author:

Lennerstrand Johan1,Hertogs Kurt2,Stammers David K.3,Larder Brendan A.1

Affiliation:

1. Virco UK, Ltd., Cambridge CB4 0GA,1 and

2. Virco N.V., B-2800 Mechelen, Belgium2

3. Structural Biology Division, The Wellcome Trust Centre for Human Genetics, University of Oxford, OX3 7BN Oxford,3 United Kingdom, and

Abstract

ABSTRACT 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 PP i 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.

Publisher

American Society for Microbiology

Subject

Virology,Insect Science,Immunology,Microbiology

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