ArticleNucleic acids research2001
Destabilization of tRNA3(Lys) from the primer-binding site of HIV-1 genome by anti-A loop polyamide nucleotide analog.
Article in Nucleic acids research, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 15 citations in OpenAlex.
- Probing the structure of human tRNARSC advances · 2023Article
- Initiation of HIV Reverse Transcription.Viruses · 2010Article
- Prospects for antisense peptide nucleic acid (PNA) therapies for HIV.Expert opinion on biological therapy · 2009Review
- The structure of the human tRNALys3 anticodon bound to the HIV genome is stabilized by modified nucleosides and adjacent mismatch base pairs.Nucleic acids research · 2009Article
- Immunological response to peptide nucleic acid and its peptide conjugate targeted to transactivation response (TAR) region of HIV-1 RNA genome.Oligonucleotides · 2008Article
- Article
- Anti-HIV-1 activity of anti-TAR polyamide nucleic acid conjugated with various membrane transducing peptides.Nucleic acids research · 2005Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Initiation of human immunodeficiency virus type 1 (HIV-1) reverse transcription occurs by extension of the cellular tRNA3(Lys) which anneals to the primer-binding site (PBS) on the 5' non-translated region of the viral RNA genome. The A-rich sequence (A-loop) upstream of the PBS interacts with the anticodon loop of tRNA3(Lys) and has been proposed to be essential for conferring specificity to tRNA3(Lys) for priming the initiation of HIV-1 reverse transcription. We observed that polyamide nucleic acid targeted to the A-loop sequence (PNAAL) exhibits high binding specificity for its target sequence. The PNAAL pre-bound to the A-loop sequence prevents tRNA3(Lys) priming on the viral RNA consequently blocking in vitro initiation of reverse transcription. Further, PNAAL can efficiently disrupt the preformed [tRNA3(Lys)--viral RNA] complex thereby rendering it non-functional for reverse transcription. The endogenous reverse transcription in disrupted HIV-1 virions containing packaged tRNA3(Lys) and its replicating enzyme RT was significantly inhibited by PNAAL, thus providing direct evidence of the involvement of the A-loop region of viral RNA genome in tRNA3(Lys) priming process. These findings suggest the potential of the A-loop region as a critical target for blocking HIV-1 replication.
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