The accuracy of reverse transcriptase from HIV-1
Abstract
A study was conducted to determine the fidelity of DNA synthesis catalyzed in vitro by the reverse transcriptase from a human immunodeficiency virus type 1 (HIV-1). Like other retroviral reverse transcriptases, the HIV-1 enzyme does not correct errors by exonucleolytic proofreading. Measurements with M13mp2-based fidelity assays indicated that the HIV-1 enzyme, isolated either from virus particles or from Escherichia coli cells infected with a plasmid expressing the cloned gene, was exceptionally inaccurate, having an average error rate per detectable nucleotide incorporated of 1/1700. It was, in fact, the least accurate reverse transcriptase described to date, one-tenth as accurate as the polymerases isolated from avian myeloblastosis or murine leukemia viruses, which have average error rates of ∼1/17,000 and ∼1/30,000, respectively. DNA sequence analyses of mutations generated by HIV-1 polymerase showed that base substitution, addition, and deletion errors were all produced. Certain template positions were mutational hotspots where the error rate could be as high as 1 per 70 polymerized nucleotides. The data are consistent with the notion that the exceptional diversity of the HIV-1 genome results from error-prone reverse transcription.
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In assays of RNA-dependent DNA synthesis, there is no significant difference in mutation rates among AMV, MLV, and HIV-1 RTs.
“Interestingly, assays designed to read mutations during RNA-dependent DNA synthesis reveal no significant difference in mutation rates among AMV, MLV, and HIV-1 RTs, indicating that HIV-1 RT’s misincorporation rate is higher during DNA-dependent DNA synthesis (Roberts et al. 1988, Boyer et al. 1992, Ji and Loeb 1992, Yu and Goodman 1992, Bakhanashvili and Hizi 1993, Kerr and Anderson 1997).”
From Beyond reverse transcription: molecular mechanisms and emerging paradigms in retroviral replication (2026) · cites this paper as Roberts et al. 1988
In cell-free assays of DNA-dependent DNA synthesis, AMV and MLV RTs introduce nearly 10-fold fewer mutations than HIV-1 RT.
“Based on cell-free assays designed to read mutations during DNA-dependent DNA synthesis, it has been shown that AMV and MLV RTs introduce nearly 10-fold fewer mutations when compared to HIV-1 RT (Roberts et al. 1988, 1989, Barrioluengo et al. 2012).”
From Beyond reverse transcription: molecular mechanisms and emerging paradigms in retroviral replication (2026) · cites this paper as Roberts et al. 1988
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Beyond reverse transcription: molecular mechanisms and emerging paradigms in retroviral replication
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“…difference in mutation rates among AMV, MLV, and HIV-1 RTs, indicating that HIV-1 RT’s misincorporation rate is higher during DNA-dependent DNA synthesis (Roberts et al. 1988 , Boyer et al. 1992 , Ji and Loeb 1992 , Yu and Goodman 1992 , Bakhanashvili and Hizi 1993 , Kerr and Anderson 1997 ).”
- Authors
- Roberts, J. D., Bebenek, K., & Kunkel, T. A.
- Affiliations
- National Institutes of Health (US)
- Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709.
- Venue
- Science
- Published
- 1988-11-25
- Volume
- 242
- Issue
- 4882
- Pages
- 1171-1173
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2065740427
- Cited by
- 997
- References
- 1
- Citations by year
- 2026: 4 · 2025: 15 · 2024: 15 · 2023: 14 · 2022: 22 · 2021: 14 · 2020: 21 · 2019: 13 · 2018: 22 · 2017: 32 · 2016: 28 · 2015: 31 · 2014: 27 · 2013: 35 · 2012: 38
- FWCI
- 7.66
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
- Health Sciences › Medicine › Infectious Diseases › HIV/AIDS drug development and treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Evolution and Genetic Dynamics
- Keywords
- HIV-1 reverse transcriptase, error rate, DNA synthesis fidelity, exonuclease proofreading, mutational hotspots, insertion and deletion errors, viral genome diversity, retroviral evolution
- MeSH terms
- DNA, DNA-Directed DNA Polymerase, Electrophoresis, Polyacrylamide Gel, Escherichia coli, Exonucleases, HIV, Moloney murine leukemia virus, Mutation, Avian Myeloblastosis Virus, Nucleotides, Recombinant Proteins, RNA-Directed DNA Polymerase
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