ArticleJournal of virology1999
Genetic instability of live, attenuated human immunodeficiency virus type 1 vaccine strains.
Article in Journal of virology, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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.
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
36 citing papers in PubMed, 84 citations in OpenAlex.
- Article
- Understanding the performance of HIV-1 viral vector vaccines: adenovirus and poxvirus case studies.Frontiers in immunology · 2025Review
- Viral attenuation by engineered protein fragmentation.Virus evolution · 2018Article
- Transmissible Viral Vaccines.Trends in microbiology · 2018Review
- A Protocol for the Production of Integrase-deficient Lentiviral Vectors for CRISPR/Cas9-mediated Gene Knockout in Dividing Cells.Journal of visualized experiments : JoVE · 2017Article
- Arresting Evolution.Trends in genetics : TIG · 2017Review
- Integrase-Deficient Lentiviral Vector as an All-in-One Platform for Highly Efficient CRISPR/Cas9-Mediated Gene Editing.Molecular therapy. Methods & clinical development · 2017Article
- Synthetic biology approach for the development of conditionally replicating HIV-1 vaccine.Journal of chemical technology and biotechnology (Oxford, Oxfordshire : 1986) · 2017Article
- Tet-On Systems For Doxycycline-inducible Gene Expression.Current gene therapy · 2016Review
- Evolutionary reversion of live viral vaccines: Can genetic engineering subdue it?Virus evolution · 2015Article
- Article
- HIV-1 Escape From RNAi Antivirals: Yet Another Houdini Action?Molecular therapy. Nucleic acids · 2012Article
- The HIV-1 Tat protein has a versatile role in activating viral transcription.Journal of virology · 2011Article
- Current progress in the development of a prophylactic vaccine for HIV-1.Drug design, development and therapy · 2010Review
- Divergence, not diversity of an attenuated equine lentivirus vaccine strain correlates with protection from disease.Vaccine · 2010Article
- HIV-1 evolution: frustrating therapies, but disclosing molecular mechanisms.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2010Review
- Possible applications for replicating HIV 1 vectors.HIV therapy · 2010Article
- HIV vaccine: it may take two to tango, but no party time yet.Retrovirology · 2009Article
- Toward a durable anti-HIV gene therapy based on RNA interference.Annals of the New York Academy of Sciences · 2009Review
- HIV evades RNA interference directed at TAR by an indirect compensatory mechanism.Cell host & microbe · 2008Article
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 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Live, attenuated viruses have been the most successful vaccines in monkey models of human immunodeficiency virus type 1 (HIV-1) infection. However, there are several safety concerns about using such an anti-HIV vaccine in humans, including reversion of the vaccine strain to virulence and recombination with endogenous retroviral sequences to produce new infectious and potentially pathogenic viruses. Because testing in humans would inevitably carry a substantial risk, we set out to test the genetic stability of multiply deleted HIV constructs in perpetuated tissue culture infections. The Delta3 candidate vaccine strain of HIV-1 contains deletions in the viral long terminal repeat (LTR) promoter and the vpr and nef genes. This virus replicates with delayed kinetics, but a profound enhancement of virus replication was observed after approximately 2 months of culturing. Analysis of the revertant viral genome indicated that the three introduced deletions were maintained but a 39-nucleotide sequence was inserted in the LTR promoter region. This insert was formed by duplication of the region encoding three binding sites for the Sp1 transcription factor. The duplicated Sp1 region was demonstrated to increase the LTR promoter activity, and a concomitant increase in the virus replication rate was measured. In fact, duplication of the Sp1 sites increased the fitness of the Delta3 virus (Vpr/Nef/U3) to levels higher than that of the singly deleted DeltaVpr virus. These results indicate that deleted HIV-1 vaccine strains can evolve into fast-replicating variants by multiplication of remaining sequence motifs, and their safety is therefore not guaranteed. This insight may guide future efforts to develop more stable anti-HIV vaccines.
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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.