PMID: 9525609Apr 3, 1998Paper

The impact of multidideoxynucleoside resistance-conferring mutations in human immunodeficiency virus type 1 reverse transcriptase on polymerase fidelity and error specificity

Journal of Virology
L RezendeV R Prasad

Abstract

Variants of human immunodeficiency virus type 1 (HIV-1) that are highly resistant to a number of nucleoside analog drugs have been shown to develop in some patients receiving 2',3'-dideoxy-3'-azidothymidine therapy in combination with 2',3'-dideoxycytidine or 2',3'-dideoxyinosine. The appearance, in the reverse transcriptase (RT), of the Q151M mutation in such variants precedes the sequential appearance of three or four additional mutations, resulting in a highly resistant virus. Three of the affected residues are proposed to lie in the vicinity of the template-primer in the three-dimensional structure of the HIV-1 RT-double-stranded DNA complex. The amino acid residue Q151 is thought to be very near the templating base. The nucleoside analog resistance mutations in the beta9-beta10 (M184V) and the beta5a (E89G) strands of HIV-1 RT were previously shown to increase the fidelity of deoxynucleoside triphosphate insertion. Therefore, we have examined wild-type HIV-1BH10 RT and two nucleoside analog-resistant variants, the Q151M and A62V/V75I/F77L/F116Y/Q151M (VILYM) RTs, for their overall forward mutation rates in an M13 gapped-duplex assay that utilizes lacZ alpha as a reporter. The overall error rates for the wild-type, the Q151...Continue Reading

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Citations

Jul 12, 2005·Antiviral Chemistry & Chemotherapy·Prem L SharmaRaymond F Schinazi
Mar 29, 2000·Proceedings of the National Academy of Sciences of the United States of America·P L BoyerS H Hughes
Mar 21, 2000·Medicinal Research Reviews·H JonckheereE De Clercq
Jun 17, 2008·The Journal of Antimicrobial Chemotherapy·Anne DeracheAnne-Geneviève Marcelin
Jun 25, 2015·Microbiology Spectrum·Stephen H Hughes
Feb 16, 2011·Journal of Molecular Biology·Varuni K Jamburuthugoda, Thomas H Eickbush

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