ArticleRetrovirology2006
Modification of the Tet-On regulatory system prevents the conditional-live HIV-1 variant from losing doxycycline-control.
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.
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Who cites it
25 citing papers in PubMed.
- HIV-1 N-myristoylation-dependent hijacking of late endosomes/lysosomes to drive Gag assembly in macrophages.Journal of cell science · 2024Article
- CRISPR-Cas attack of HIV-1 proviral DNA can cause unintended deletion of surrounding cellular DNA.Journal of virology · 2023Article
- Opposing roles of CLK SR kinases in controlling HIV-1 gene expression and latency.Retrovirology · 2022Article
- Article
- Impact of Nuclear Export Pathway on Cytoplasmic HIV-1 RNA Transport Mechanism and Distribution.mBio · 2020Article
- HIV-1 Gag Forms Ribonucleoprotein Complexes with Unspliced Viral RNA at Transcription Sites.Viruses · 2020Article
- CRISPR-Cas9 Dual-gRNA Attack Causes Mutation, Excision and Inversion of the HIV-1 Proviral DNA.Viruses · 2020Article
- An activator of G protein-coupled receptor and MEK1/2-ERK1/2 signaling inhibits HIV-1 replication by altering viral RNA processing.PLoS pathogens · 2020Article
- Cardiac glycoside/aglycones inhibit HIV-1 gene expression by a mechanism requiring MEK1/2-ERK1/2 signaling.Scientific reports · 2018Article
- HIV-1 enhances mTORC1 activity and repositions lysosomes to the periphery by co-opting Rag GTPases.Scientific reports · 2017Article
- Controlling Multicycle Replication of Live-Attenuated HIV-1 Using an Unnatural Genetic Switch.ACS synthetic biology · 2017Article
- Modulation of the splicing regulatory function of SRSF10 by a novel compound that impairs HIV-1 replication.Nucleic acids research · 2017Article
- Synthetic biology approach for the development of conditionally replicating HIV-1 vaccine.Journal of chemical technology and biotechnology (Oxford, Oxfordshire : 1986) · 2017Article
- Identification of small molecule modulators of HIV-1 Tat and Rev protein accumulation.Retrovirology · 2017Article
- Article
- Characterization of novel inhibitors of HIV-1 replication that function via alteration of viral RNA processing and rev function.Nucleic acids research · 2013Article
- Digoxin suppresses HIV-1 replication by altering viral RNA processing.PLoS pathogens · 2013Article
- A doxycycline-dependent human immunodeficiency virus type 1 replicates in vivo without inducing CD4+ T-cell depletion.The Journal of general virology · 2012Article
- Differential effects of hnRNP D/AUF1 isoforms on HIV-1 gene expression.Nucleic acids research · 2012Article
- Differential effect of CLK SR Kinases on HIV-1 gene expression: potential novel targets for therapy.Retrovirology · 2011Article
Corrections and comments
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Authors and funding
4 authors.
Funding
No grant is acknowledged in the PubMed record.
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.
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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.