ArticleProceedings of the National Academy of Sciences of the United States of America2007
HIV-susceptible transgenic rats allow rapid preclinical testing of antiviral compounds targeting virus entry or reverse transcription.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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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.
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Who cites it
23 citing papers in PubMed, 48 citations in OpenAlex.
- Advances in Genome Editing and Application to the Generation of Genetically Modified Rat Models.Frontiers in genetics · 2021Review
- Absence of cGAS-mediated type I IFN responses in HIV-1-infected T cells.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- HIV-associated synaptic degeneration.Molecular brain · 2017Review
- Vpx overcomes a SAMHD1-independent block to HIV reverse transcription that is specific to resting CD4 T cells.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- HIV-associated neurocognitive disorder--pathogenesis and prospects for treatment.Nature reviews. Neurology · 2016Review
- Antibody and antiretroviral preexposure prophylaxis prevent cervicovaginal HIV-1 infection in a transgenic mouse model.Journal of virology · 2013Article
- SAMHD1 restricts HIV-1 infection in resting CD4(+) T cells.Nature medicine · 2012Article
- Rodent models for HIV-associated neurocognitive disorders.Trends in neurosciences · 2012Review
- Molecular design, functional characterization and structural basis of a protein inhibitor against the HIV-1 pathogenicity factor Nef.PloS one · 2011Article
- High natural permissivity of primary rabbit cells for HIV-1, with a virion infectivity defect in macrophages as the final replication barrier.Journal of virology · 2010Article
- Endogenous CD317/Tetherin limits replication of HIV-1 and murine leukemia virus in rodent cells and is resistant to antagonists from primate viruses.Journal of virology · 2010Article
- Long-lasting enfuvirtide carrier pentasaccharide conjugates with potent anti-human immunodeficiency virus type 1 activity.Antimicrobial agents and chemotherapy · 2010Article
- Pharmacovirological impact of an integrase inhibitor on human immunodeficiency virus type 1 cDNA species in vivo.Journal of virology · 2009Article
- Recent advancements for the evaluation of anti-viral activities of natural products.New biotechnology · 2009Review
- Expression of Human CD4 and chemokine receptors in cotton rat cells confers permissiveness for productive HIV infection.Virology journal · 2009Article
- Article
- Mouse T-cells restrict replication of human immunodeficiency virus at the level of integration.Retrovirology · 2008Article
- Article
- Relief of preintegration inhibition and characterization of additional blocks for HIV replication in primary mouse T cells.PloS one · 2008Article
- Aqueous extracts from peppermint, sage and lemon balm leaves display potent anti-HIV-1 activity by increasing the virion density.Retrovirology · 2008Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
The current testing of anti-HIV drugs is hampered by the lack of a small animal that is readily available and easy to handle; can be infected systemically with HIV type 1 (HIV-1); harbors the major HIV-1 target cells in a physiological frequency, organ distribution, and activation state; and is established as a pharmacological model. Here, we explored the potential of outbred Sprague-Dawley rats that transgenically express the HIV-1 receptor complex on CD4 T cells and macrophages as a model for the preclinical evaluation of inhibitors targeting virus entry or reverse transcription. The concentrations of the peptidic fusion inhibitor enfuvirtide or the nonnucleoside reverse transcriptase inhibitor efavirenz required to inhibit HIV-1 infection of cultured primary CD4 T cells and macrophages from human CD4 and CCR5-transgenic rats differed by no more than 3-fold from those required for human reference cultures. Prophylactic treatment of double-transgenic rats with a weight-adapted pediatric dosing regimen for either enfuvirtide (s.c., twice-daily) or efavirenz (oral, once-daily) achieved a 92.5% or 98.8% reduction, respectively, of the HIV-1 cDNA load in the spleen 4 days after i.v. HIV-1 challenge. Notably, a once-daily dosing regimen for enfuvirtide resulted in a approximately 5-fold weaker inhibition of infection, unmasking the unfavorable pharmacokinetic characteristics of the synthetic peptide in the context of an efficacy trial. This work provides proof of principle that HIV-susceptible transgenic rats can allow a rapid and predictive preclinical evaluation of the inhibitory potency and of the pharmacokinetic properties of antiviral compounds targeting early steps in the HIV replication cycle.
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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.