ArticleAIDS (London, England)2018
An advanced BLT-humanized mouse model for extended HIV-1 cure studies.
Article in AIDS (London, England), 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 71 citations in OpenAlex.
- The promise and perils of humanized mice: workshop report from the 29th scientific conference of the society on NeuroImmune pharmacology (SNIP).NeuroImmune pharmacology and therapeutics · 2025Article
- Examining Chronic Inflammation, Immune Metabolism, and T Cell Dysfunction in HIV Infection.Viruses · 2024Review
- CD47;Rag2;IL-2rγ triple knock-out mice pre-conditioning with busulfan could be a novel platform for generating hematopoietic stem cells engrafted humanized mice.Frontiers in immunology · 2024Article
- Progress in building clinically relevant patient-derived tumor xenograft models for cancer research.Animal models and experimental medicine · 2023Review
- Current Advances in Humanized Mouse Models for Studying NK Cells and HIV Infection.Microorganisms · 2023Review
- The Humanized Mouse Model: What Added Value Does It Offer for HIV Research?Pathogens (Basel, Switzerland) · 2023Review
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- SARS-CoV-2 Variant-Specific Infectivity and Immune Profiles Are Detectable in a Humanized Lung Mouse Model.Viruses · 2022Article
- Three-dimensional models of the cervicovaginal epithelia to study host-microbiome interactions and sexually transmitted infections.Pathogens and disease · 2022Article
- Purine nucleoside phosphorylase enables dual metabolic checkpoints that prevent T cell immunodeficiency and TLR7-associated autoimmunity.The Journal of clinical investigation · 2022Article
- Type I interferons and TGF-β cooperate to induce liver fibrosis during HIV-1 infection under antiretroviral therapy.JCI insight · 2022Article
- HIV Latency in Myeloid Cells: Challenges for a Cure.Pathogens (Basel, Switzerland) · 2022Review
- Baseline and time-updated factors in preclinical development of anionic dendrimers as successful anti-HIV-1 vaginal microbicides.Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnology · 2022Review
- Novel Humanized Peripheral Blood Mononuclear Cell Mouse Model with Delayed Onset of Graft-versus-Host Disease for Preclinical HIV Research.Journal of virology · 2022Article
- Latency reversal plus natural killer cells diminish HIV reservoir in vivo.Nature communications · 2022Article
- Learning to Be Elite: Lessons From HIV-1 Controllers and Animal Models on Trained Innate Immunity and Virus Suppression.Frontiers in immunology · 2022Review
- Inducing Long-Term HIV-1 Latency in the TKO-BLT Mouse Model.Methods in molecular biology (Clifton, N.J.) · 2022Article
- ApoA-I mimetics reduce systemic and gut inflammation in chronic treated HIV.PLoS pathogens · 2022Article
- SRSF1 acts as an IFN-I-regulated cellular dependency factor decisively affecting HIV-1 post-integration steps.Frontiers in immunology · 2022Article
Corrections and comments
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Authors and funding
16 authors at 3 institutions in 2 countries.
Funding
Abstract
objectiveAlthough bone marrow, liver, thymus (BLT)-humanized mice provide a robust model for HIV-1 infection and enable evaluation of cure strategies dependent on endogenous immune responses, most mice develop graft versus host disease (GVHD), limiting their utility for extended HIV cure studies. This study aimed to: evaluate the GVHD-resistant C57 black 6 (C57BL/6) recombination activating gene 2 (Rag2)γcCD47 triple knockout (TKO)-BLT mouse as a model to establish HIV-1 latency. Determine whether TKO-BLT mice could be maintained on antiretroviral therapy (ART) for extended periods of time. Assess the rapidity of viral rebound following therapy interruption.
designTKO-BLT mice were HIV-1 infected, treated with various ART regimens over extended periods of time and assayed for viral rebound following therapy interruption.
methodsDaily subcutaneous injection and oral ART-mediated suppression of HIV-1 infection was tested at various doses in TKO-BLT mice. Mice were monitored for suppression of viremia and cellular HIV-1 RNA and DNA prior to and following therapy interruption.
resultsMice remained healthy for 45 weeks posthumanization and could be treated with ART for up to 18 weeks. Viremia was suppressed to less than 200 copies/ml in the majority of mice with significant reductions in cellular HIV-1 RNA and DNA. Treatment interruption resulted in rapid viral recrudescence.
conclusionHIV-1 latency can be maintained in TKO-BLT mice over extended periods on ART and rapid viral rebound occurs following therapy removal. The additional 15-18 weeks of healthy longevity compared with other BLT models provides sufficient time to examine the decay kinetics of the latent reservoir as well as observe delays in recrudescence in HIV-1 cure studies.
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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.