ArticleNucleic acids research2007
Purine analog substitution of the HIV-1 polypurine tract primer defines regions controlling initiation of plus-strand DNA synthesis.
Article in Nucleic acids research, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 23 citations in OpenAlex.
- Non-integrase mechanisms for dolutegravir resistance.Retrovirology · 2026Review
- HIV-1 3΄ polypurine tract mutations and integrase inhibitor resistance.AIDS (London, England) · 2025Review
- C G composition in transposon-derived genes is increased in FXD with perturbed immune system.NAR molecular medicine · 2024Article
- HIV-1 3'-Polypurine Tract Mutations Confer Dolutegravir Resistance by Switching to an Integration-Independent Replication Mechanism via 1-LTR Circles.Journal of virology · 2023Article
- Dynamic bulge nucleotides in the KSHV PAN ENE triple helix provide a unique binding platform for small molecule ligands.Nucleic acids research · 2021Article
- Mechanism of polypurine tract primer generation by HIV-1 reverse transcriptase.The Journal of biological chemistry · 2018Article
- SiRNA-induced mutation in HIV-1 polypurine tract region and its influence on viral fitness.PloS one · 2015Article
- Targeting the HIV RNA genome: high-hanging fruit only needs a longer ladder.Current topics in microbiology and immunology · 2015Review
- Recent findings on the mechanisms involved in tenofovir resistance.Antiviral chemistry & chemotherapy · 2014Review
- Probing Retroviral and Retrotransposon Genome Structures: The "SHAPE" of Things to Come.Molecular biology international · 2012Article
- Reverse transcriptase in motion: conformational dynamics of enzyme-substrate interactions.Biochimica et biophysica acta · 2010Review
- Article
- Ribonuclease H: properties, substrate specificity and roles in retroviral reverse transcription.The FEBS journal · 2009Review
- Article
- Extensive purifying selection acting on synonymous sites in HIV-1 Group M sequences.Virology journal · 2008Review
- The effects of alternate polypurine tracts (PPTs) and mutations of sequences adjacent to the PPT on viral replication and cleavage specificity of the Rous sarcoma virus reverse transcriptase.Journal of virology · 2008Article
- RNase H activity: structure, specificity, and function in reverse transcription.Virus research · 2008Review
- Article
- High-resolution NMR analysis of the conformations of native and base analog substituted retroviral and LTR-retrotransposon PPT primers.Chemistry & biology · 2008Article
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Despite extensive study, the mechanism by which retroviral reverse transciptases (RTs) specifically utilize polypurine tract (PPT) RNA for initiation of plus-strand DNA synthesis remains unclear. Three sequence motifs within or adjacent to the purine-rich elements are highly conserved, namely, a rU:dA tract region immediately 5' to the PPT, an rA:dT-rich sequence constituting the upstream portion of the PPT and a downstream rG:dC tract. Using an in vitro HIV-1 model system, we determined that the former two elements define the 5' terminus of the (+)-strand primer, whereas the rG:dC tract serves as the primary determinant of initiation specificity. Subsequent analysis demonstrated that G-->A or A-->G substitution at PPT positions -2, -4 and +1 (relative to the scissile phosphate) substantially reduces (+)-strand priming. We explored this observation further using PPT substrates substituted with a variety of nucleoside analogs [inosine (I), purine riboside (PR), 2-aminopurine (2-AP), 2,6-diaminopurine (2,6-DAP), isoguanine (iG)], or one of the naturally occurring bases at these positions. Our results demonstrate that for PPT positions -2 or +1, substituting position 2 of the purine was an important determinant of cleavage specificity. In addition, cleavage specificity was greatly affected by substituting -4G with an analog containing a 6-NH2 moiety.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.