ArticleProceedings of the National Academy of Sciences of the United States of America1994
Hypermutagenesis of RNA using human immunodeficiency virus type 1 reverse transcriptase and biased dNTP concentrations.
Article in Proceedings of the National Academy of Sciences of the United States of America, 1994. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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Who cites it
56 citing papers in PubMed.
- Mapping of susceptibility loci for Ebola virus pathogenesis in mice.Cell reports · 2024Article
- Host-dependent editing of SARS-CoV-2 in COVID-19 patients.Emerging microbes & infections · 2021Article
- Development of a User-Friendly Pipeline for Mutational Analyses of HIV Using Ultra-Accurate Maximum-Depth Sequencing.Viruses · 2021Article
- Hypermutations in porcine respiratory and reproductive syndrome virus.Canadian journal of veterinary research = Revue canadienne de recherche veterinaire · 2019Article
- Increasing the CpG dinucleotide abundance in the HIV-1 genomic RNA inhibits viral replication.Retrovirology · 2017Article
- HIV-1 tolerates changes in A-count in a small segment of the pol gene.Retrovirology · 2017Article
- dUTPase: the frequently overlooked enzyme encoded by many retroviruses.Retrovirology · 2015Review
- HIV-1 and HIV-2 exhibit similar mutation frequencies and spectra in the absence of G-to-A hypermutation.Retrovirology · 2015Article
- The impact of HIV-1 genetic diversity on the efficacy of a combinatorial RNAi-based gene therapy.Gene therapy · 2015Article
- Possible footprints of APOBEC3F and/or other APOBEC3 deaminases, but not APOBEC3G, on HIV-1 from patients with acute/early and chronic infections.Journal of virology · 2014Article
- In vivo HIV-1 hypermutation and viral loads among antiretroviral-naive Brazilian patients.AIDS research and human retroviruses · 2014Article
- The impact of unprotected T cells in RNAi-based gene therapy for HIV-AIDS.Molecular therapy : the journal of the American Society of Gene Therapy · 2014Article
- Basis for early and preferential selection of the E138K mutation in HIV-1 reverse transcriptase.Antimicrobial agents and chemotherapy · 2013Article
- Effect of mutations at position E138 in HIV-1 reverse transcriptase and their interactions with the M184I mutation on defining patterns of resistance to nonnucleoside reverse transcriptase inhibitors rilpivirine and etravirine.Antimicrobial agents and chemotherapy · 2013Article
- The biased nucleotide composition of the HIV genome: a constant factor in a highly variable virus.Retrovirology · 2012Review
- Absence of HIV-1 evolution in the gut-associated lymphoid tissue from patients on combination antiviral therapy initiated during primary infection.PLoS pathogens · 2012Article
- Ribavirin can be mutagenic for arenaviruses.Journal of virology · 2011Article
- HIV-1 modulates the tRNA pool to improve translation efficiency.Molecular biology and evolution · 2011Article
- Article
- Specific and nonspecific host adaptation during arboviral experimental evolution.Journal of molecular microbiology and biotechnology · 2011Review
Corrections and comments
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Authors and funding
3 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The finding of G-->A hypermutated retroviral genomes in which up to 40% of guanines may be substituted by adenines was proposed to result from the depletion of the intracellular dCTP concentration and suggested a means to hypermutagenize nucleic acids. Using a RNA/reverse transcriptase ratio of approximately 1:30, comparable to that within the retroviral replication complex, G-->A hypermutants were produced in a simple in vitro reaction using highly biased dNTP concentrations--i.e., a low ratio of [dCTP]/[dTTP]. Up to 38% of G residues could be substituted, the proportion being inversely proportional to the concentration of dCTP. As G-->A hypermutation resulted from elongation beyond multiple rG.dT mismatches, U-->C hypermutants resulting from multiple rU.dG mismatches were sought, and found, during cDNA synthesis using low [dATP] and high [dGTP]. Mixed G-->A and U-->C hypermutants could also be produced under conditions of low [dCTP] plus low [dATP] and high [dTTP] plus high [dGTP]. Hypermutagenesis should allow jumping through, and subsequent exploration of, sequence space to a greater degree than heretofore and, in conjunction with genetic screening, might be of use in the search of proteins or ribozymes with novel or enhanced properties.
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