ArticleJournal of virology2000
Identification of a key target sequence to block human immunodeficiency virus type 1 replication within the gag-pol transframe domain.
Article in Journal of virology, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
What it found
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Who cites it
9 citing papers in PubMed, 48 citations in OpenAlex.
- Inhibition of human immunodeficiency virus replication by cell membrane-crossing oligomers.Molecular medicine (Cambridge, Mass.) · 2012Article
- Article
- Design of embedded chimeric peptide nucleic acids that efficiently enter and accurately reactivate gene expression in vivo.Proceedings of the National Academy of Sciences of the United States of America · 2010Article
- Prospects for antisense peptide nucleic acid (PNA) therapies for HIV.Expert opinion on biological therapy · 2009Review
- Molecular characterization of the HIV-1 gag nucleocapsid gene associated with vertical transmission.Retrovirology · 2006Article
- Potent antiviral activity of north-methanocarbathymidine against Kaposi's sarcoma-associated herpesvirus.Antimicrobial agents and chemotherapy · 2005Article
- Discovery of small-molecule human immunodeficiency virus type 1 entry inhibitors that target the gp120-binding domain of CD4.Journal of virology · 2005Article
- Anti-TAR polyamide nucleotide analog conjugated with a membrane-permeating peptide inhibits human immunodeficiency virus type 1 production.Journal of virology · 2002Article
- Resistance to nucleoside analog reverse transcriptase inhibitors mediated by human immunodeficiency virus type 1 p6 protein.Journal of virology · 2001Article
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 2 countries.
Funding
Abstract
Although the full sequence of the human immunodeficiency virus type 1 (HIV-1) genome has been known for more than a decade, effective genetic antivirals have yet to be developed. Here we show that, of 22 regions examined, one highly conserved sequence (ACTCTTTGGCAACGA) near the 3' end of the HIV-1 gag-pol transframe region, encoding viral protease residues 4 to 8 and a C-terminal Vpr-binding motif of p6(Gag) protein in two different reading frames, can be successfully targeted by an antisense peptide nucleic acid oligomer named PNA(PR2). A disrupted translation of gag-pol mRNA induced at the PNA(PR2)-annealing site resulted in a decreased synthesis of Pr160(Gag-Pol) polyprotein, hence the viral protease, a predominant expression of Pr55(Gag) devoid of a fully functional p6(Gag) protein, and the excessive intracellular cleavage of Gag precursor proteins, hindering the processes of virion assembly. Treatment with PNA(PR2) abolished virion production by up to 99% in chronically HIV-1-infected H9 cells and in peripheral blood mononuclear cells infected with clinical HIV-1 isolates with the multidrug-resistant phenotype. This particular segment of the gag-pol transframe gene appears to offer a distinctive advantage over other regions in invading viral structural genes and restraining HIV-1 replication in infected cells and may potentially be exploited as a novel antiviral genetic target.
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Registered trials
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.