Evolution of AZT resistance in HIV-1: the 41-70 intermediate that is not observed in vivo has a replication defect

Virology
R E JeeningaBen Berkhout

Abstract

The human immunodeficiency virus type 1 (HIV-1) is notorious for its ability to evolve drug-resistance in patients treated with potent antivirals. Resistance to inhibitors of the viral reverse transcriptase (RT) enzyme is frequently mediated by a single amino acid substitution within RT. Resistance against the nucleoside analogue AZT is remarkable in that multiple amino acid changes accumulate over time to yield virus variants with high-level drug resistance. We now report that in addition to drug-resistance properties, the relative replication capacity of the virus variants affects the evolution of AZT resistance. Some of the typical AZT-resistance mutations have a negative impact on virus replication, and the 41-70 double mutant was found to represent a particularly poor virus. Furthermore, introduction of additional AZT-resistance mutations (41-70-215) leads to nearly complete restoration of virus replication. These results may explain the absence of the 41-70 double mutant in clinical samples and indicate that the evolution of AZT resistance is also influenced by virus replication parameters. Prolonged passage of the replication-impaired 41-70 virus in the absence of AZT yielded several fast-replicating variants. These reve...Continue Reading

References

Mar 1, 1992·Proceedings of the National Academy of Sciences of the United States of America·P KellamB A Larder
Jul 1, 1995·Antimicrobial Agents and Chemotherapy·P L Boyer, S H Hughes
Oct 13, 1995·The Journal of Biological Chemistry·E O Freed, M A Martin
May 1, 1996·Journal of Acquired Immune Deficiency Syndromes and Human Retrovirology : Official Publication of the International Retrovirology Association·A ClelandA J Brown
Sep 1, 1996·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·R LingT J Harrison
Feb 14, 1998·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·M MelegariJ R Wands
Jun 10, 1998·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·M I AllenL D Condreay
Nov 25, 1998·Proceedings of the National Academy of Sciences of the United States of America·M NijhuisJ Albert
Mar 3, 1999·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·S K Ono-NitaM Omata

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Citations

Sep 21, 2010·Nature Structural & Molecular Biology·Xiongying TuEddy Arnold
Jan 12, 2013·Proceedings of the National Academy of Sciences of the United States of America·Zhinan JinKlaus Klumpp
Feb 3, 2009·AIDS Research and Human Retroviruses·Maria TrignettiFrancesca Ceccherini-Silberstein
Aug 20, 2005·Journal of Computational Biology : a Journal of Computational Molecular Cell Biology·Niko BeerenwinkelThomas Lengauer
May 28, 2010·Journal of Virology·Toshiyuki MiuraBruce D Walker
May 29, 2004·Pharmacogenomics·Wilma ZiebuhrThomas Dandekar
Apr 23, 2013·Current Opinion in Virology·Kalyan Das, Eddy Arnold
Feb 22, 2008·Virus Research·Javier Martinez-Picado, Miguel Angel Martínez
Feb 17, 2006·Journal of Medical Virology·Elijah PaintsilLouis Alexander
Jan 31, 2019·The Journal of Biological Chemistry·Dirk EgginkRogier W Sanders
Jan 29, 2021·Chemical Reviews·Maria E CilentoStefan G Sarafianos

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