“Binding, bending and bonding”: polypurine tract-primed initiation of plus-strand DNA synthesis in human immunodeficiency virus
Abstract
During the course of reverse transcription, human immunodeficiency virus type 1 reverse transcriptase (HIV-1 RT) initiates plus-strand DNA synthesis from two highly conserved, purine-rich RNA segments of the viral genome referred to as the 3' and central polypurine tracts (3' and cPPTs). Processing of these elements occurs in several sequential steps including (1) minus-strand DNA synthesis over the PPT(s), (2) ribonuclease H (RNase H) mediated cleavage at the PPT 3' terminus, (3) plus-strand DNA synthesis from the nascent RNA primer(s), and (4) primer removal. Completing each of these steps precisely and specifically is essential, as failure to do so can result in reduced virus replication and/or impaired integration of viral DNA into the host cell genome. In this review, plus-strand primer processing in HIV-1 is discussed from biochemical, structural, and historical perspectives. A comparative analysis of PPT-processing in different LTR-containing retroelements is also presented.
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All retroviruses contain a polypurine tract (PPT) near the 3′ end of the viral genome, upstream of the U3 region, consisting of fewer than 20 ribonucleotides including stretches of adenines and guanines.
“Similar to the PBS, all retroviruses contain a polypurine tract (PPT) near the 3′ end of the viral genome, upstream of the U3 region (Fig. 3). The PPT consists of fewer than 20 ribonucleotides, including stretches of adenines and guanines (Huber and Richardson 1990, Coffin 1997, Rausch and Le Grice 2004).”
From Beyond reverse transcription: molecular mechanisms and emerging paradigms in retroviral replication (2026) · cites this paper as Rausch and Le Grice 2004
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- Authors
- Rausch, J. W., & Le Grice, S. F. J.
- Affiliations
- Frederick National Laboratory for Cancer Research (US)
- ORCID
- Rausch, Jason W
- Venue
- The International Journal of Biochemistry & Cell Biology
- Publisher
- Elsevier BV
- Published
- 2004-09
- Volume
- 36
- Issue
- 9
- Pages
- 1752-1766
- ISSN
- 1357-2725 (ISSN-L)
- OpenAlex
- W2091884906
- Cited by
- 106
- References
- 73
- Citations by year
- 2026: 4 · 2025: 2 · 2024: 2 · 2023: 3 · 2022: 4 · 2021: 2 · 2020: 1 · 2019: 4 · 2018: 7 · 2017: 4 · 2016: 1 · 2015: 9 · 2014: 4 · 2013: 11 · 2012: 6
- FWCI
- 0.73
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The International Journal of Biochemistry & Cell Biology (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 › Immunology and Microbiology › Immunology › T-cell and Retrovirus Studies
- Keywords
- HIV-1 reverse transcriptase, polypurine tract, plus-strand DNA synthesis, reverse transcription initiation, RNase H, primer removal, viral integration
- MeSH terms
- DNA, Viral, Purines, Sequence Homology, Nucleic Acid, HIV-1, Ribonuclease H, HIV Reverse Transcriptase
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