This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Mansky, L. M.
Right arrow Articles by Bernard, L. C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Mansky, L. M.
Right arrow Articles by Bernard, L. C.

 Previous Article  |  Next Article 

Journal of Virology, October 2000, p. 9532-9539, Vol. 74, No. 20
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

3'-Azido-3'-Deoxythymidine (AZT) and AZT-Resistant Reverse Transcriptase Can Increase the In Vivo Mutation Rate of Human Immunodeficiency Virus Type 1

Louis M. Mansky* and Lisa C. Bernard

Department of Molecular Virology, Immunology, and Medical Genetics, Center for Retrovirus Research, and Comprehensive Cancer Center, Ohio State University Medical Center, Columbus, Ohio 43210

Received 11 May 2000/Accepted 28 July 2000

How antiretroviral drug resistance influences human immunodeficiency virus type 1 (HIV-1) evolution is not clear. This study tested the hypothesis that antiretroviral drugs such as 3'-azido-3'-deoxythymidine (AZT) can influence the in vivo mutation rate of HIV-1. It was observed that AZT can increase the rate of HIV-1 mutation by a factor of 7 in a single round of replication. In addition, (-)2',3'-dideoxy-3'-thiacytidine (3TC) was also found to increase the mutation rate of HIV-1 by a factor of 3. It was also found that HIV-1 drug-resistant reverse transcriptase (RT) variants can influence the in vivo mutation rate. Replication of HIV-1 with AZT-resistant RTs increased the mutation rate by as much as a factor of 3, while replication of HIV-1 with a 3TC-resistant RT (M184V) had no significant effect on the mutation rate. It was observed that only high-level, AZT-resistant RT variants could influence the in vivo mutation rate (i.e., M41L/T215Y and M41L/D67N/K70R/T215Y). In total, these observations indicate that both antiretroviral drugs and drug resistance mutations can influence the in vivo mutation rate of HIV-1.

* Corresponding author. Mailing address: Department of Molecular Virology, Immunology, and Medical Genetics, 2078 Graves Hall, 333 W. 10th Ave., Columbus, OH 43210. Phone: (614) 292-5525. Fax: (614) 292-9805. E-mail: mansky.3{at}osu.edu.

Journal of Virology, October 2000, p. 9532-9539, Vol. 74, No. 20
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Dapp, M. J., Clouser, C. L., Patterson, S., Mansky, L. M. (2009). 5-Azacytidine Can Induce Lethal Mutagenesis in Human Immunodeficiency Virus Type 1. J. Virol. 83: 11950-11958 [Abstract] [Full Text]  
  • Bampi, C., Bibillo, A., Wendeler, M., Divita, G., Gorelick, R. J., Le Grice, S. F. J., Darlix, J.-L. (2006). Nucleotide Excision Repair and Template-independent Addition by HIV-1 Reverse Transcriptase in the Presence of Nucleocapsid Protein. J. Biol. Chem. 281: 11736-11743 [Abstract] [Full Text]  
  • Curr, K., Tripathi, S., Lennerstrand, J., Larder, B. A., Prasad, V. R. (2006). Influence of naturally occurring insertions in the fingers subdomain of human immunodeficiency virus type 1 reverse transcriptase on polymerase fidelity and mutation frequencies in vitro. J. Gen. Virol. 87: 419-428 [Abstract] [Full Text]  
  • Althaus, C. L., Bonhoeffer, S. (2005). Stochastic Interplay between Mutation and Recombination during the Acquisition of Drug Resistance Mutations in Human Immunodeficiency Virus Type 1. J. Virol. 79: 13572-13578 [Abstract] [Full Text]  
  • Chen, R., Yokoyama, M., Sato, H., Reilly, C., Mansky, L. M. (2005). Human Immunodeficiency Virus Mutagenesis during Antiviral Therapy: Impact of Drug-Resistant Reverse Transcriptase and Nucleoside and Nonnucleoside Reverse Transcriptase Inhibitors on Human Immunodeficiency Virus Type 1 Mutation Frequencies. J. Virol. 79: 12045-12057 [Abstract] [Full Text]  
  • Nikolenko, G. N., Palmer, S., Maldarelli, F., Mellors, J. W., Coffin, J. M., Pathak, V. K. (2005). Mechanism for nucleoside analog-mediated abrogation of HIV-1 replication: Balance between RNase H activity and nucleotide excision. Proc. Natl. Acad. Sci. USA 102: 2093-2098 [Abstract] [Full Text]  
  • Mbisa, J. L., Nikolenko, G. N., Pathak, V. K. (2005). Mutations in the RNase H Primer Grip Domain of Murine Leukemia Virus Reverse Transcriptase Decrease Efficiency and Accuracy of Plus-Strand DNA Transfer. J. Virol. 79: 419-427 [Abstract] [Full Text]  
  • Nikolenko, G. N., Svarovskaia, E. S., Delviks, K. A., Pathak, V. K. (2004). Antiretroviral Drug Resistance Mutations in Human Immunodeficiency Virus Type 1 Reverse Transcriptase Increase Template-Switching Frequency. J. Virol. 78: 8761-8770 [Abstract] [Full Text]  
  • Jewell, N. A., Chen, R., Raices, R., Mansky, L. M. (2003). Nucleoside reverse transcriptase inhibitors and HIV mutagenesis. J Antimicrob Chemother 52: 547-550 [Full Text]  
  • Mansky, L. M., Le Rouzic, E., Benichou, S., Gajary, L. C. (2003). Influence of Reverse Transcriptase Variants, Drugs, and Vpr on Human Immunodeficiency Virus Type 1 Mutant Frequencies. J. Virol. 77: 2071-2080 [Abstract] [Full Text]  
  • Grande-Perez, A., Sierra, S., Castro, M. G., Domingo, E., Lowenstein, P. R. (2002). From the Cover: Molecular indetermination in the transition to error catastrophe: Systematic elimination of lymphocytic choriomeningitis virus through mutagenesis does not correlate linearly with large increases in mutant spectrum complexity. Proc. Natl. Acad. Sci. USA 99: 12938-12943 [Abstract] [Full Text]  
  • Mansky, L. M., Pearl, D. K., Gajary, L. C. (2002). Combination of Drugs and Drug-Resistant Reverse Transcriptase Results in a Multiplicative Increase of Human Immunodeficiency Virus Type 1 Mutant Frequencies. J. Virol. 76: 9253-9259 [Abstract] [Full Text]  
  • Zhang, W.-H., Svarovskaia, E. S., Barr, R., Pathak, V. K. (2002). Y586F mutation in murine leukemia virus reverse transcriptase decreases fidelity of DNA synthesis in regions associated with adenine-thymine tracts. Proc. Natl. Acad. Sci. USA 99: 10090-10095 [Abstract] [Full Text]  
  • Boyer, P. L., Sarafianos, S. G., Arnold, E., Hughes, S. H. (2001). Selective Excision of AZTMP by Drug-Resistant Human Immunodeficiency Virus Reverse Transcriptase. J. Virol. 75: 4832-4842 [Abstract] [Full Text]  
  • Diamond, T. L., Kimata, J., Kim, B. (2001). Identification of a Simian Immunodeficiency Virus Reverse Transcriptase Variant with Enhanced Replicational Fidelity in the Late Stage of Viral Infection. J. Biol. Chem. 276: 23624-23631 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»