Evidence map›Paper›PMID 17094796›Full record

ArticleRetrovirology2006

Modification of the Tet-On regulatory system prevents the conditional-live HIV-1 variant from losing doxycycline-control.

Xue Zhou, Monique Vink, Ben Berkhout, Atze T Das

Abstract read
In one paragraph

Article in Retrovirology, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

25 citing papers in PubMed.

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  13. Synthetic biology approach for the development of conditionally replicating HIV-1 vaccine.Journal of chemical technology and biotechnology (Oxford, Oxfordshire : 1986) · 2017
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors.

Xue ZhouLaboratory of Experimental Virology, Department of Medical Microbiology, Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center of the University of Amsterdam, Meibergdreef 15, 1105 AZ Amsterdam, The Netherlands. x.zhou@amc.uva.nl
Monique Vink
Ben Berkhout
Atze T Das

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundWe have previously constructed a doxycycline (dox)-dependent HIV-1 variant by incorporating the Tet-On gene regulatory system into the viral genome. Replication of this HIV-rtTA virus is driven by the dox-inducible transactivator protein rtTA, and can be switched on and off at will. We proposed this conditional-live virus as a novel vaccine approach against HIV-1. Upon vaccination, replication of HIV-rtTA can be temporarily activated by transient dox administration and controlled to the extent needed for optimal induction of the immune system. However, subsequent dox-withdrawal may impose a selection for virus variants with reduced dox-dependence.

resultsWe simulated this on/off switching of virus replication in multiple, independent cultures and could indeed select for HIV-rtTA variants that replicated without dox. Nearly all evolved variants had acquired a typical amino acid substitution at position 56 in the rtTA protein. We developed a novel rtTA variant that blocks this undesired evolutionary route and thus prevents HIV-rtTA from losing dox-control.

conclusionThe loss of dox-control observed upon evolution of the dox-dependent HIV-1 variant was effectively blocked by modification of the Tet-On regulatory system.

Indexed as

Binding SitesDoxycyclineEvolution, MolecularGene Expression Regulation, ViralGene Products, tatGenes, BacterialGenetic EngineeringHIV-1Mutagenesis, Site-DirectedMutation, MissenseOperator Regions, GeneticPhenotypetat Gene Products, Human Immunodeficiency VirusVirus ReplicationDoxycyclineGene Products, tattat Gene Products, Human Immunodeficiency Virus

Identifiers

PMID17094796
PMCPMC1637113

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Registered trials

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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.