ArticleJournal of virology2003
Human immunodeficiency virus type 1 protease regulation of tat activity is essential for efficient reverse transcription and replication.
Article in Journal of virology, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
16 citing papers in PubMed, 1 synthesis or guideline pooled it, 33 citations in OpenAlex.
- HIV Genome-Wide Protein Associations: a Review of 30 Years of Research.Microbiology and molecular biology reviews : MMBR · 2016Pooled it
- A Tripartite Complex HIV-1 Tat-Cyclophilin A-Capsid Protein Enables Tat Encapsidation That Is Required for HIV-1 Infectivity.Journal of virology · 2023Article
- Y44A Mutation in the Acidic Domain of HIV-2 Tat Impairs Viral Reverse Transcription and LTR-Transactivation.International journal of molecular sciences · 2020Article
- Vehicles of intercellular communication: exosomes and HIV-1.The Journal of general virology · 2019Review
- Semen Exosomes Promote Transcriptional Silencing of HIV-1 by Disrupting NF-κB/Sp1/Tat Circuitry.Journal of virology · 2018Article
- A mutant tat protein inhibits HIV-1 reverse transcription by targeting the reverse transcription complex.Journal of virology · 2015Article
- Retrospective on the all-in-one retroviral nucleocapsid protein.Virus research · 2014Review
- Anti-tat Hutat2:Fc mediated protection against tat-induced neurotoxicity and HIV-1 replication in human monocyte-derived macrophages.Journal of neuroinflammation · 2014Article
- Dynamic interactions of the HIV-1 Tat with nucleic acids are critical for Tat activity in reverse transcription.Nucleic acids research · 2014Article
- Comparative nucleic acid chaperone properties of the nucleocapsid protein NCp7 and Tat protein of HIV-1.Virus research · 2012Review
- In vivo selection of CD4(+) T cells transduced with a gamma-retroviral vector expressing a single-chain intrabody targeting HIV-1 tat.Human gene therapy · 2012Article
- The RNA annealing mechanism of the HIV-1 Tat peptide: conversion of the RNA into an annealing-competent conformation.Nucleic acids research · 2011Article
- Potent inhibition of HIV-1 replication by a Tat mutant.PloS one · 2009Article
- HIV-1 Tat C-terminus is cleaved by calpain 1: implication for Tat-mediated neurotoxicity.Biochimica et biophysica acta · 2009Article
- Construction of a doxycycline-dependent simian immunodeficiency virus reveals a nontranscriptional function of tat in viral replication.Journal of virology · 2007Article
- HIV-1 protease and reverse transcriptase control the architecture of their nucleocapsid partner.PloS one · 2007Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The human immunodeficiency virus type 1 (HIV-1) Tat protein enhances reverse transcription, but it is not known whether Tat acts directly on the reverse transcription complex or through indirect mechanisms. Since processing of Tat by HIV protease (PR) might mask its presence and, at least in part, explain this lack of data, we asked whether Tat can be cleaved by PR. We used a rabbit reticulocyte lysate (RRL) system to make Tat and PR. HIV-1 PR is expressed as a Gag-Pol fusion protein, and a PR-inactivated Gag-Pol is also expressed as a control. We showed that Tat is specifically cleaved in the presence of PR, producing a protein of approximately 5 kDa. This result suggested that the cleavage site was located in or near the Tat basic domain (amino acids 49 to 57), which we have previously shown to be important in reverse transcription. We created a panel of alanine-scanning mutations from amino acids 45 to 54 in Tat and evaluated functional parameters, including transactivation, reverse transcription, and cleavage by HIV-1 PR. We showed that amino acids 49 to 52 (RKKR) are absolutely required for Tat function in reverse transcription, that mutation of this domain blocks cleavage by HIV-1 PR, and that other pairwise mutations in this region modulate reverse transcription and proteolysis in strikingly similar degrees. Mutation of Tat Y47G48 to AA also down-regulated Tat-stimulated reverse transcription but had little effect on transactivation or proteolysis by HIV PR, suggesting that Y47 is critical for reverse transcription. We altered the tat gene of the laboratory strain NL4-3 to Y47D and Y47N so that overlapping reading frames were not affected and showed that Y47D greatly diminished virus replication and conveyed a reverse transcription defect. We hypothesize that a novel, cleaved form of Tat is present in the virion and that it requires Y47 for its role in support of efficient reverse transcription.
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Registered trials
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