ArticleProceedings of the National Academy of Sciences of the United States of America2001
In vitro evolution of a highly replicating, doxycycline-dependent HIV for applications in vaccine studies.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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41 citing papers in PubMed, 82 citations in OpenAlex.
- HIV-1 Gag Forms Ribonucleoprotein Complexes with Unspliced Viral RNA at Transcription Sites.Viruses · 2020Article
- Genetic variation and function of the HIV-1 Tat protein.Medical microbiology and immunology · 2019Review
- Improving miRNA Delivery by Optimizing miRNA Expression Cassettes in Diverse Virus Vectors.Human gene therapy methods · 2017Review
- Controlling Multicycle Replication of Live-Attenuated HIV-1 Using an Unnatural Genetic Switch.ACS synthetic biology · 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
- A doxycycline-dependent human immunodeficiency virus type 1 replicates in vivo without inducing CD4+ T-cell depletion.The Journal of general virology · 2012Article
- Article
- Cotranscriptional Chromatin Remodeling by Small RNA Species: An HTLV-1 Perspective.Leukemia research and treatment · 2012Article
- Retroviral replicating vectors in cancer.Methods in enzymology · 2012Article
- The HIV-1 Tat protein has a versatile role in activating viral transcription.Journal of virology · 2011Article
- EBV LMP1, a viral mimic of CD40, activates dendritic cells and functions as a molecular adjuvant when incorporated into an HIV vaccine.Journal of leukocyte biology · 2011Article
- Latent Membrane Protein 1 as a molecular adjuvant for single-cycle lentiviral vaccines.Retrovirology · 2011Article
- Anti-viral opportunities during transcriptional activation of latent HIV in the host chromatin.Methods (San Diego, Calif.) · 2011Review
- Improved Tet-responsive promoters with minimized background expression.BMC biotechnology · 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
- Autoregulatory lentiviral vectors allow multiple cycles of doxycycline-inducible gene expression in human hematopoietic cells in vivo.Gene therapy · 2010Article
- Optimization of the doxycycline-dependent simian immunodeficiency virus through in vitro evolution.Retrovirology · 2008Article
- HIV-1 latency in actively dividing human T cell lines.Retrovirology · 2008Article
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
A major concern associated with the use of vaccines based on live-attenuated viruses is the possible and well documented reversion to pathogenic phenotypes. In the case of HIV, genomic deletions or mutations introduced to attenuate viral pathogenicity can be repaired by selection of compensating mutations. These events lead to increased virus replication rates and, eventually, disease progression. Because replication competence and degree of protection appear to be directly correlated, further attenuation of a vaccine virus may compromise the ability to elicit a protective immune response. Here, we describe an approach toward a safe attenuated HIV vaccine. The system is not based on permanent reduction of infectivity by alteration of important viral genomic sequences, but on strict control of replication through the insertion of the tetracycline (Tet) system in the HIV genome. Furthermore, extensive in vitro evolution was applied to the prototype Tet-controlled HIV to select for variants with optimized rather than diminished replication capacity. The final product of evolution has properties uniquely suited for use as a vaccine strain. The evolved virus is highly infectious, as opposed to a canonically attenuated virus. It replicates efficiently in T cell lines and in activated and unstimulated peripheral blood mononuclear cells. Most importantly, replication is strictly dependent on the nontoxic Tetanalogue doxycycline and can be turned on and off. These results suggest that this in vitro evolved, doxycycline-dependent HIV might represent a useful tool toward the development of a safer, live-attenuated HIV vaccine.
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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.